Orosomucoid Proteins Interact with the Small Subunit of ... · PDF file4 Palmitoyltransferase...

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RESEARCH ARTICLE 1 2 Orosomucoid Proteins Interact with the Small Subunit of Serine 3 Palmitoyltransferase and Contribute to Sphingolipid Homeostasis and Stress 4 Responses in Arabidopsis 5 6 Jian Li*, Jian Yin*, Chan Rong*, Kai-En Li*, Jian-Xin Wu*, Li-Qun Huang, Hong-Yun Zeng, Sunil 7 Kumar Sahu, Nan Yao† 8 9 State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Resources, School of 10 Life Sciences, Sun Yat-sen University, Guangzhou 510275, P. R. China 11 *These authors contributed equally to this work. 12 †Corresponding Author: [email protected] 13 14 Short title: ORMs play a vital role in sphingolipid regulation 15 16 One-sentence summary: Loss-of-function of the orosomucoid proteins stimulate the de novo 17 biosynthesis of sphingolipids, cause an early senescence phenotype, and enhance resistance to oxidative 18 stress and pathogen infection. 19 20 The author responsible for distribution of materials integral to the findings presented in this article in 21 accordance with the policy described in the Instructions for Authors (www.plantcell.org) is: Nan Yao 22 ([email protected]) 23 24 ABSTRACT 25 Serine palmitoyltransferase (SPT), a pyridoxyl-5′-phosphate-dependent enzyme, catalyzes the first and 26 rate-limiting step in sphingolipid biosynthesis. In humans and yeast, orosomucoid proteins (ORMs) 27 negatively regulate SPT and thus play an important role in maintaining sphingolipid levels. Despite the 28 importance of sphingoid intermediates as bioactive molecules, the regulation of sphingolipid biosynthesis 29 through SPT is not well understood in plants. Here, we identified and characterized the Arabidopsis 30 thaliana ORMs, ORM1 and ORM2. Loss-of-function of both ORM1 and ORM2 (orm1 amiR-ORM2) 31 stimulated de novo sphingolipid biosynthesis, leading to strong sphingolipid accumulation, especially of 32 long-chain bases and ceramides. Yeast two-hybrid, bimolecular fluorescence complementation, and 33 coimmunoprecipitation assays confirmed that ORM1 and ORM2 physically interact with the small 34 subunit of SPT (ssSPT), indicating that ORMs inhibit ssSPT function. We found that orm1 amiR-ORM2 35 plants exhibited an early-senescence phenotype accompanied by H2O2 production at the cell wall and in 36 mitochondria, active vesicular trafficking, and formation of cell wall appositions. Strikingly, the orm1 37 amiR-ORM2 plants showed increased expression of genes related to endoplasmic reticulum stress and 38 defenses, and also had enhanced resistance to oxidative stress and pathogen infection. Taken together, our 39 findings indicate that ORMs interact with SPT to regulate sphingolipid homeostasis and play a pivotal 40 role in environmental stress tolerance in plants. 41

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Plant Cell Advance Publication. Published on December 6, 2016, doi:10.1105/tpc.16.00574

©2016 American Society of Plant Biologists. All Rights Reserved

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INTRODUCTION 43

In eukaryotes, sphingolipids make up ~40% of the lipids of the plasma membrane and are 44

also abundant in other endomembranes. The functions of these key lipids have been intensively 45

investigated in mammals and yeast for decades (Hannun and Obeid, 2008) and recent work has 46

begun to explore sphingolipid biochemistry in plants. Sphingolipids play pivotal roles as 47

membrane structural components, as bioactive molecules involved in signal transduction and cell 48

regulation, and in a wide range of other biological processes including secretion, programmed 49

cell death, autophagy, stress responses, and cell-cell interactions (Liang et al., 2003; Markham et 50

al., 2011; Sentelle et al., 2012; Bi et al., 2014; Li et al., 2015; Wu et al., 2015). On the outer 51

leaflet of the membrane, sphingolipids form membrane microdomains with cholesterol to 52

provide conformational support for membrane proteins and serve as a platform for recruitment of 53

signaling molecules (Lingwood and Simons, 2010). 54

In humans, changes in sphingolipid contents have been closely linked to diabetes 55

(Summers and Nelson, 2005), cancer (Modrak et al., 2006), Alzheimer’s disease (Mizuno et al., 56

2016), cardiovascular disease, and respiratory disease (Park et al., 2006). For example, 57

sphingosine-1-phosphate can bind to the G protein-coupled receptor EDG5 to inhibit the activity 58

of Rac protein, which could prevent the metastasis of tumor cells (Okamoto et al., 2000). The 59

sphingosine-1-phosphate analog fingolimod (FTY720) has a similar activity and can be used for 60

cancer treatment (Brinkmann et al., 2010). Sphingolipids also function in plant development and 61

responses to biotic or abiotic stresses (Chen et al., 2006; Dietrich et al., 2008; Teng et al., 2008; 62

Chen et al., 2009; Markham et al., 2011; Ternes et al., 2011; König et al., 2012; Zhang et al., 63

2013; Bi et al., 2014). 64

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Regulation of the levels of sphingolipids involves the modulation of key enzymes such as 65

ceramide synthases, ceramidases, ceramide kinase, glucosylceramidase, and 66

inositolphosphorylceramidase (Liang et al., 2003; Wang et al., 2008; Ternes et al., 2011; Bi et al., 67

2014 ; Li et al., 2015; Msanne et al., 2015; Wu et al., 2015). Serine palmitoyltransferase (SPT) is 68

a pyridoxyl-5′-phosphate-dependent enzyme that catalyzes the first and rate-limiting step in 69

sphingolipid biosynthesis, the condensation between L-serine and a long-chain acyl thioester 70

such as palmitoyl-CoA (C16-CoA) to generate long-chain bases (LCBs) (Chen et al., 2006). In 71

Arabidopsis, the SPT enzyme has three subunits, LCB1, LCB2a, and LCB2b. The fbr11-2/lcb1-1 72

mutant, a loss-of-function mutation of LCB1, shows abnormal development, initiating apoptotic 73

cell death in binucleate microspores, and the LCB2 loss-function mutant displays gametophytic 74

lethality (Chen et al., 2006; Dietrich et al., 2008; Teng et al., 2008). 75

Work in animals and yeast showed that orosomucoid (ORM) proteins can modulate SPT 76

activity (Breslow et al., 2010; Han et al., 2010; Gururaj et al., 2013). The ORM family proteins 77

are endoplasmic reticulum (ER)-resident membrane proteins encoded by ORM or ORMDL genes, 78

which are conserved from yeast to humans (Hjelmqvist et al., 2002; Moffatt et al., 2007). 79

Depletion of the mammalian ORMDL1-3 eliminates the feedback of exogenous ceramide on 80

ceramide biosynthesis, indicating that ORMDL proteins function as the primary regulators of 81

ceramide biosynthesis in mammalian cells (Siow and Wattenberg, 2012). In yeast, genetic studies 82

established a link between ORM1 and ORM2 and sphingolipid metabolism, as deletion of ORM1 83

and ORM2 leads to toxic accumulation of sphingolipids, whereas overexpression of ORM1 or 84

ORM2 leads to reduced sphingolipid levels (Breslow et al., 2010). Thus, ORM1 and ORM2 85

negatively regulate sphingolipid synthesis. 86

Yeast (Saccharomyces cerevisiae) Orm proteins regulate sphingolipid metabolism by 87

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forming a multiprotein complex with SPT, termed the SPOTS complex, which also contains the 88

SPT accessory subunit Tsc3 and the phosphoinositide phosphatase Sac1. Phosphorylation of 89

Orm proteins, mediated by both branches of the TOR signaling pathway, regulates SPT activity 90

to maintain sphingolipid homeostasis (Breslow et al., 2010; Han et al., 2010; Breslow et al., 91

2013). The Ypk1 protein kinase, downstream of rapamycin complex TORC, regulates Orm1 and 92

Orm2 phosphorylation (Roelants et al., 2011; Berchtold et al., 2012; Niles et al., 2012; Sun et al., 93

2012; Shimobayashi et al., 2013). Orm proteins’ SPT-inhibitory activity is subject to feedback 94

regulation by multiple sphingolipid intermediates, including LCBs, ceramide, and complex 95

sphingolipids. When sphingolipid biosynthesis is disrupted, phosphorylation of their amino 96

termini activates Orm1 and Orm2, thus enabling a compensatory increase in SPT activity 97

(Breslow et al., 2010; Liu et al., 2012). Orm1 activity is adjusted in response to manipulation of 98

Orm2 expression levels, with increased Orm2 expression causing a corresponding increase in 99

Orm1 phosphorylation and vice versa. Phosphoregulation of Orm proteins controls sphingolipid 100

biosynthesis in response to various stresses, including heat stress, ER stress, iron stress, and cell 101

wall stress (Sun et al., 2012; Lee et al., 2012; Gururaj et al., 2013). 102

In addition to ORM, eukaryotes have a class of polypeptides, the SPT small subunits 103

(ssSPT), which can regulate SPT activity. For example, yeast has an 80-amino acid polypeptide 104

called Tsc3, which combines with the LCB1 and LCB2 subunits to form a trimer, thereby 105

activating SPT (Gable et al., 2000). Humans have two ssSPT: ssSPTa (68 amino acids) and 106

ssSPTb (76 amino acids). Co-expression of human ssSPTa or ssSPTb and LCB1 or LCB2a, 107

LCB2b can activate SPT in yeast lcb1 lcb2△ mutants (Han et al., 2009). Recent work reported 108

that Arabidopsis has two ssSPTs, encoded by ssSPTa (At1g06515) and ssSPTb (At2g30942). 109

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These 56-amino acid ssSPTs can activate SPT and play an important role in the formation of 110

mature pollen (Kimberlin et al., 2013). 111

Considerable progress has been made in advancing our knowledge of plant sphingolipid 112

metabolism in the past 10-15 years. However, our understanding of ORMs, particularly in plants, 113

remains in its infancy. Here we reported functional characterization of the ORM genes (ORM1, 114

AT1G01230; ORM2, AT5G42000) in Arabidopsis thaliana. We discovered that ORM can 115

interact with and inhibit ssSPT, thus affecting sphingolipid levels. Our studies strongly suggest 116

that ORM plays a key role in the plant response to biotic and abiotic stress. 117

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RESULTS 119

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Loss of ORM1 and ORM2 Function Causes an Early-Senescence Phenotype and High 121

Sphingolipid Accumulation 122

ORM family genes encode conserved ER membrane proteins in eukaryotic cells. 123

Arabidopsis thaliana has two genes encoding homologs of S. cerevisiae Orm, AT1G01230 and 124

AT5G42000, designated ORM1 and ORM2 (Figure 1A), which encode 157- and 154-amino-acid 125

polypeptides with 39% and 35% identity to Orm1 in yeast, respectively (Supplemental Figure 126

1A). Using the TMHMM protein structure analysis tool 127

(http://www.cbs.dtu.dk/services/TMHMM/), we found that ORM1 and ORM2 have three 128

predicted transmembrane domains (Supplemental Figure 2). The N-terminal extension found in 129

yeast was absent from Arabidopsis ORMs, but phosphorylation site analysis (using NetPhos and 130

the plant-specific algorithm PhosPhAt), showed ORM1 and ORM2 to have possible 131

phosphorylation sites (Supplemental Figure 1A). ORM1 and ORM2 were expressed at higher 132

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levels in siliques than in other tissues (Supplemental Figure 1B). Our confocal microscopy 133

observations confirmed that ORM1 and ORM2 localized to the ER of Arabidopsis (Figure 1D). 134

To test the function of the Arabidopsis ORMs, we characterized the available T-DNA 135

mutant lines for these genes: SALK_046054 (predicted T-DNA insertion in the first intron of 136

ORM1), and SAIL_1286_D09 (predicted T-DNA insertion in the 5′ UTR of ORM2). 137

Homozygous lines were identified for each of these mutants. We did not detect the full-length 138

transcript of ORM1 in SALK_046054, indicating that the line is a null mutant (Supplemental 139

Figures 1C and 1E). In Arabidopsis, according to TAIR (http://www.arabidopsis.org), ORM2 has 140

two splice isoforms, AT5G42000.1 and AT5G42000.2. However, our RT-PCR experiments 141

detected only the transcripts of AT5G42000.1 (ORM2.1) in plants (Supplemental Figure 1D). 142

Since the full-length transcript of ORM2 was still detected in SAIL_1286_D09 (Supplemental 143

Figure 1D), we also generated an artificial micro RNA (amiR) line targeting ORM2 (amiR-144

ORM2) (Supplemental Figure 1E). For subsequent analysis, we crossed orm1 with amiR-ORM2 145

plants and obtained the orm1 amiR-ORM2 homozygous lines. In addition, we placed ORM1 or 146

ORM2 cDNAs under control of the cauliflower mosaic virus 35S (CaMV35S) promoter to create 147

the overexpression lines ORM1-OX and ORM2-OX in Arabidopsis (Supplemental Figures 1C 148

and 1D). The orm1 amiR-ORM2 plants initially underwent the same development as wild type 149

(Supplemental Figure 3A, top panel, orm1 amiR-ORM2-6 and orm1 amiR-ORM2-5). However, 150

in late development, the orm1 amiR-ORM2 plants showed accelerated senescence, characterized 151

by early chlorosis of rosette leaf tips (Figure 1B and 1C). By contrast, the development of the 152

orm1 single mutant and amiR-ORM2 plants was similar to that of wild-type plants 153

(Supplemental Figure 3A). 154

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In yeast, Orm proteins act as negative mediators of sphingolipid biosynthesis by 155

inhibiting SPT activity (Han et al., 2010). To determine the role of ORM1 and ORM2 in the 156

regulation of sphingolipid biosynthesis in Arabidopsis, we comprehensively analyzed the major 157

classes of sphingolipids in orm1 and amiR-ORM2 plants. We observed no obvious changes in 158

sphingolipids in orm1 and amiR-ORM2 plants compared with wild type (Supplemental Figure 159

3B). However, the sphingolipid profile of 28-day-old orm1 amiR-ORM2 plants showed a 160

dramatic increase in the total sphingolipid contents, especially in LCBs (~15-fold) and ceramides 161

(8-fold), compared with the wild type. By contrast, the amount of glucosylceramides did not 162

change relative to wild type (Figure 1E). Among LCBs, we noticed that d18:0 LCB showed the 163

largest difference in orm1 amiR-ORM2 (Supplemental Figure 4). Remarkably, the ceramide 164

backbones containing long-chain fatty acids (C16) exhibited a more dramatic increase than 165

ceramide containing very-long-chain fatty acids (VLCFA) (C20, C24 and C26) (Supplemental 166

Figure 4). 167

We also measured the sphingolipid contents of orm1 amiR-ORM2 and wild-type rosettes 168

at different developmental stages, and the results showed a gradual accumulation of 169

sphingolipids in orm1 amiR-ORM2 plants (Supplemental Figure 5). The sphingolipid profile of 170

21-day-old plants revealed that the total amounts of LCB, ceramides, and hydroxyceramides 171

were higher in orm1 amiR-ORM2 plants, compared to wild-type plants. However, no visible 172

early-senescence phenotype was observed in the orm1 amiR-ORM2 plants at this stage 173

(Supplemental Figure 3). In other words, orm1 amiR-ORM2 plants accumulated sphingolipids 174

prior to the early senescence. There were no significant changes in sphingolipids in orm1 175

mutants, amiR-ORM2 plants, or overexpression transgenic plants with respect to wild-type plants 176

at different developmental stages (Supplemental Figures 3 and 5). These results indicated that 177

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ORM1 and ORM2 negatively co-regulate sphingolipid biosynthesis in plants. In addition, the 178

early-senescence phenotype of orm1 amiR-ORM2 plants was associated with over-accumulation 179

of sphingolipids. 180

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ORMs Suppress the de novo Biosynthesis of Sphingolipids in Arabidopsis 182

To decipher the possible cause of the over-accumulation of sphingolipids, we used 15N-183

labeling and metabolic turnover analysis to directly measure in vivo sphingolipid changes, as we 184

reported previously (Shi et al., 2015). Seven-day-old orm1 amiR-ORM2 and wild-type seedlings 185

were transferred to N-deficient ½x MS liquid medium containing 5 mM 15N- serine in a time 186

course. Isotope-labeled LCBs and ceramides of orm1 amiR-ORM2 plants accumulated to 187

significant levels after 24 h of incubation with 15N-serine, relative to wild-type and orm1 or 188

amiR-ORM2 plants (Figure 2). It is noteworthy that the increase of 15N-labeled d18:0 LCB was 189

greater than that of t18:0 LCB (Figure 2). In addition to quantitative changes in ceramides, d18:0 190

ceramides showed a more dramatic increase than t18:0 ceramides (Figure 2). The initial LCB 191

produced in plants is dihydrosphingosine (d18:0 LCB) (Chen et al., 2009). Hence, these 192

measurements confirmed our hypothesis that the loss of ORM1 and ORM2 function in the orm1 193

amiR-ORM2 plants promotes the de novo biosynthesis of sphingolipids, and ultimately leads to 194

higher accumulation of sphingolipids. Moreover, the higher levels of 15N-labeled ceramides 195

containing C16 fatty acid in orm1 amiR-ORM2 plants (Figure 2) were consistent with 196

accumulation of C16 ceramides in 28-day-old orm1 amiR-ORM2 plants (Supplemental Figure 4). 197

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ORM1 and ORM2 Interact with ssSPT 199

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Previous studies in yeast and mammals showed that ORM proteins physically interact with 200

Lcb1 and Lcb2 (Han et al., 2010). To test the interactions of ORM proteins in Arabidopsis, we 201

first applied yeast two-hybrid assays. Surprisingly, our yeast two-hybrid assays revealed that the 202

ORM proteins physically interact with the small subunit of SPT (ssSPT) (Figure 3A). The 203

interaction was further confirmed by co-immunoprecipitation (co-IP) assays. Anti-Flag resins 204

could precipitate not only ORM-Flag but also GFP-ssSPT (Figure 3B). When free GFP was used 205

as a control, no GFP signals were detected in the eluate (Figure 3B). We also used bimolecular 206

fluorescence complementation (BiFC) assays to confirm the ORM-ssSPT interaction. Clear YFP 207

fluorescence was observed in protoplasts co-transformed with pSATN-nEYFP-ORM1 and 208

pSATN-cEYFP-ssSPTa or pSATN-cEYFP-ssSPTb, pSATN-nEYFP-ORM2, and pSATN-cEYFP-209

ssSPTa or pSATN-cEYFP-ssSPTb constructs (Figure 3C). However, no YFP signal was detected 210

in the protoplasts co-transformed with one construct in combination with an empty vector 211

(Figure 3C). In addition, our confocal microscopy observations confirmed that ssSTPa and 212

ssSTPb also localized to the ER where they interact with ORMs (Supplemental Figure 6). These 213

results are consistent with the physical interaction of ORM1 and ORM2 with ssSPTa and ssSPTb 214

at the ER. We also found that SPTs localized to ER in the orm1 amiR-ORM2 plants, as 215

confirmed by transient co-expression with 35Spro:EGFP-LCB1 or 35Spro:EGFP-LCB2a/b and an 216

ER marker, suggesting that loss of function of ORMs did not affect subcellular localization of 217

the SPT complex (Supplemental Figure 7). 218

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ORM Proteins Decrease the Biosynthesis of Sphingolipids 220

Reduced SPT activity may decrease sensitivity to fumonisin B1 (FB1) by decreasing levels 221

of cytotoxic LCBs, whereas increased SPT activity may increase sensitivity to FB1 by increasing 222

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the levels of LCBs (Shi et al., 2007; Saucedo-Garcia et al., 2011). ssSPTa/ssSPTb can strongly 223

stimulate SPT activity and increase the production of LCBs in Arabidopsis (Kimberlin et al., 224

2013). To explore the function of Arabidopsis ORMs, we grew plants on agar plates with FB1 to 225

test the significance of the interaction between ORM and ssSPT. Both ORM1-OX and ORM2-OX 226

overexpression lines showed resistance to 0.5 μM FB1, whereas the orm1 amiR-ORM2 plants 227

were highly sensitive to FB1 (Figure 4). Consistent with a previous human ORM study (Breslow 228

et al., 2010), ORM proteins thus appear to negatively regulate sphingolipid biosynthesis. 229

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Loss of ORM Proteins Increases ER Stress-Related Responses 231

To understand whether the loss of ORM proteins affects cellular ultrastructure, we fixed 232

the orm1 amiR-ORM2 leaves before the appearance of the senescence phenotype. As shown in 233

Figure 5, compared with the normal nuclei observed in the wild-type cells (Figure 5A), the orm1 234

amiR-ORM2 cells showed condensed chromatin aggregated in the perinuclear membrane, which 235

indicates dying cells (Figure 5B; Liang et al., 2003), and a large amount of tiny membrane sacs 236

close to the plasma membrane and the cell wall (Figure 5C and 5D). Interestingly, we found a 237

large cell wall apposition, a clear marker of the defense response, in the orm1 amiR-ORM2 leaf 238

cells (Figure 5E). When we used the cerium chloride method (Bi et al., 2014) to detect reactive 239

oxygen species (ROS), we observed H2O2 production on the cell wall (Figure 5G and 5H), the 240

cytosolic area close to the apoplast (Figure 5I) and in the mitochondria (Figure 5J). No cerium 241

deposits were observed in the wild-type control (Figure 5F). In the dying cells, irregular ER and 242

vacuolization were frequently observed (Figure 5K). These observations suggest that loss of 243

ORMs may induce active vesicular trafficking around the plasma membrane, and this ER stress 244

phenomenon is associated with defense responses. 245

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To support the TEM observations, we investigated the expression of genes related to ER 246

stress and defenses. Strikingly, the expression of ER stress marker genes (bZIP28, bZIP60, 247

IRE1a, and TBF1) significantly increased in orm1 amiR-ORM2 plants, compared with wild type 248

(Figure 6A). To determine whether the transcription of defense-related genes was affected in 249

plants with decreased ORM function, we analyzed the expression of salicylic acid-related and 250

pathogenesis-related (PR) genes in wild-type and orm1 amiR-ORM2 plants using RT-qPCR. The 251

orm1 amiR-ORM2 plants showed high transcript levels of these genes, such as PAD4, SID2, and 252

NPR1, compared with wild type (Figure 6B). PR1 showed especially dramatic enhancement, 253

which is highly linked to the formation of cell wall appositions. No obvious changes of those 254

genes were detected in orm1 and amiR-ORM2 plants (Figure 6). 255

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Loss of ORM Proteins Enhances Plant Resistance to Abiotic and Biotic Responses 257

Recent studies have shown that sphingolipids are involved in plant stress responses (Wang 258

et al., 2008; Peer et al., 2010; Bi et al., 2014; Li et al., 2015). The orm1 amiR-ORM2 plants 259

exhibit highly induced expression of ER stress and salicylic acid-related genes, which suggested 260

to us that we should explore the role of ORMs during abiotic and biotic stress. We first treated 261

the orm1 amiR-ORM2 plants with the oxidative stress agent methyl viologen (MV), which 262

produces reactive oxygen species (ROS). Surprisingly, orm1 amiR-ORM2 plants proved to be 263

tolerant to ROS and exhibited dramatically higher survival rates than wild type (Figure 7A and 264

7B). 265

We further inoculated orm1 amiR-ORM2 plants with the bacterial pathogen Pseudomonas 266

syringae strain DG3. The orm1 amiR-ORM2 plants showed subtle symptoms after infection and 267

proved to be relatively resistant to DG3 bacteria when compared with wild type (Figure 7C). 268

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This enhanced disease resistance was consistent with the detection of high transcript levels of 269

resistance genes in orm1 amiR-ORM2 plants. These results indicate that loss of ORM function in 270

Arabidopsis affects the plant’s response to abiotic and biotic stress. 271

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DISCUSSION 274

The orosomucoid (ORM) proteins, encoded by ORMDL (ORM) genes, are highly 275

conserved eukaryotic transmembrane proteins located in the ER (Hjelmqvist et al., 2002; Han et 276

al., 2010). The three ORMDL proteins are highly conserved in humans and yeast has two 277

homologous ORM genes (ORM1 and ORM2) with redundant functions. Compared with other 278

organisms, the extent of conservation of ORM function in plants remains unclear. In this report, 279

we characterized the two ORM genes found in Arabidopsis thaliana. Our results indicate that 280

Arabidopsis ORMs function to regulate sphingolipid biosynthesis in maintaining sphingolipid 281

homeostasis and play a role in response to abiotic and biotic stresses. 282

ORM proteins have few conserved regions, mainly located in the middle of the amino 283

acid sequence, and are generally predicted to form two to four transmembrane domains. The 284

amino acid sequences of the Arabidopsis ORMs share 81% identity and also share 35-39% 285

identity with S. cerevisiae Orm1 and Orm2 (Supplemental Figure 1), but interestingly, the 286

Arabidopsis isoforms are N-terminally truncated relative to the yeast proteins and therefore lack 287

the three serine residues that are phosphorylated by Ypk1 in the yeast proteins (Roelants et al., 288

2011). Although we found some possible phosphorylation sites in Arabidopsis ORM1 and 289

ORM2, we still do not know whether the ORMs in Arabidopsis are regulated by phosphorylation, 290

similar to yeast Orm proteins. Another possibility is that Arabidopsis ORMs may be regulated by 291

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an allosteric effect on the ORM proteins themselves, where sphingolipids trigger a change in 292

conformation within a pre-existing ORM/SPT complex rather than enhancing formation of the 293

complex (Kiefer et al., 2015). 294

Orm1 and 2 negatively regulate SPT, activating or inhibiting its activity through 295

phosphorylation and dephosphorylation (Tafesse et al., 2010). Regulation of sphingolipids and 296

Orm proteins involves a feedback mechanism; Orms regulate SPT and sphingolipid metabolites 297

such as LCBs, ceramide, and accumulated sphingoid intermediates then trigger Orm 298

dephosphorylation, which in turn downregulates sphingolipid biosynthesis (Sun et al., 2012). In 299

yeast, Orm1 and Orm2 are mainly phosphorylated by Npr1 and Ypk1, respectively (Roelants et 300

al., 2011; Sun et al., 2012; Shimobayashi et al., 2013). Besides ORMs, other polypeptides can 301

also regulate the activity of SPT, namely Tsc3 in yeast (Gable et al., 2000) and ssSPTa (68 302

amino acids) and ssSPTb (76 amino acids) in human (Han et al., 2009). The 56-amino-acid 303

ssSPTs, ssSPTa, and ssSPTb strongly stimulate Arabidopsis SPT activity when coexpressed with 304

Arabidopsis LCB1 and LCB2a or 2b in a yeast spt null mutant (Kimberlin et al., 2013). Also, 305

ssSPTa suppression lines increase the resistance to FB1, and the ssSPTa overexpression lines 306

display strong sensitivity to FB1 by increasing or decreasing SPT activity (Kimberlin et al., 307

2013). In the present study, the de novo biosynthesis of sphingolipids was activated due to loss of 308

Arabidopsis ORM function. The isotope-labeled LCBs and ceramides of orm1 amiR-ORM2 309

accumulated significantly after 24 h of incubation in 15N-labeled serine, relative to wild type, 310

which showed that ORM was indeed a negative regulator of SPT in Arabidopsis, like in human 311

and yeast. Through yeast two-hybrid system, BiFC experiments, and co-IP assays, we confirmed 312

that Arabidopsis ORMs can directly bind with the Arabidopsis ssSPTs. Based on our data, we 313

put forward two possible mechanisms for the function of ORMs (Figure 8). On the one hand, 314

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ORM protein might bind to the SPT complex through the physical interaction with ssSPT and 315

inhibit the enzyme activity of SPT, rather than changing its localization; on the other hand, the 316

interaction between ORM and ssSPT might reduce the available ssSPTs that can interact with 317

core LCB1/LCB2. We favor the first mechanism, in which ORM binds to the SPT complex with 318

the ssSPT interaction, based on a recent study by Kimberlin et al (2016). In addition, we 319

observed that the ORMs and ssSPT localize in the ER, which could be the site where they 320

interact (Figure 1 and Supplemental Figure 6). Moreover, during FB1 treatment, ORM-321

overexpression lines displayed strong resistance to FB1, the opposite effect to that of ssSPTa. 322

Taking these results together, we speculate that ORMs could modulate sphingolipid levels by 323

inhibiting the function of ssSPTs in Arabidopsis. When the ORMs are knocked out, SPT could 324

be activated without changing its location, resulting in substantial accumulation of sphingolipids 325

(Figure 8). 326

Like in humans and yeast, ORM proteins in Arabidopsis play an important role in 327

maintaining the level of sphingolipids (Tafesse et al., 2010; Breslow et al., 2010; Liu et al., 2012). 328

In this study, we analyzed the ORM1 T-DNA insertion mutant orm1 and the ORM2 silencing line 329

(amiR-ORM2). Under normal growth conditions, these plants showed no obvious differences 330

compared to wild type. However, the orm1 amiR-ORM2 plants exhibited premature senescence 331

and considerable changes in sphingolipid contents, including multiple-fold increases in overall 332

sphingolipids, especially in LCBs and ceramides. Among these, d18:0 and t18:0 LCB, the 333

ceramide backbones containing long-chain fatty acids (C16) exhibited the largest changes. 334

Measurements of the sphingolipid contents of orm1 amiR-ORM2 and wild-type rosettes at 335

different developmental stages showed that prior to the onset of the early-senescence phenotype, 336

the total LCB, ceramides, and hydroxyceramides, mainly ceramide backbones containing 337

15

dihydroxy LCBs and C16 fatty acids, increased in orm1 amiR-ORM2 plants compared with wild-338

type plants. These observations suggest that LCBs or ceramides may induce plant senescence, 339

and accumulate to threshold levels due to loss of ORM function. 340

Sphingolipids are involved in the regulation of plant responses to biotic and abiotic stresses. 341

Our previous studies showed that the Arabidopsis neutral ceramidase mutant ncer1 accumulates 342

hydroxyceramides and is sensitive to oxidative stress (Li et al., 2015) and the ceramide kinase 343

mutant acd5 accumulates ceramides and is sensitive to Pseudomonas syringae and Botrytis 344

cinerea (Liang et al., 2003; Bi et al., 2014). In addition, the fatty acid α hydroxylase mutant fah1 345

fah2 has a stronger resistance to Diplodia powdery mildew and Verticillium fungi (Verticillium 346

longisporum) compared to wild type (Konig et al., 2012). In this study, we found that plants with 347

loss of ORM function are more resistant to MV and pathogen infection. This phenomenon could 348

be attributed to the higher accumulation of LCBs in the ORMs mutants compared with the acd5 349

and fah1 fah2 mutants. Several previous studies reported that LCBs play an important role 350

during abiotic and biotic stress (Peer et al., 2010; Saucedo-Garcia et al., 2011; Li et al., 2015). 351

LCBs can induce MPK6 expression and programmed cell death by an MPK6-mediated signal 352

transduction pathway (Saucedo-Garcia et al., 2011). The expression of MPK6 can be induced 353

rapidly by Flg22, which mediates the pathogen-associated pattern-induced basal resistance 354

(Galletti et al., 2011). Phytosphingosine content has been reported to rapidly escalate at two 355

hours after Pseudomonas inoculation, and is also involved in plant resistance (Peer et al., 2010). 356

Our sphingolipid data also showed an increase in the phytosphingosine contents in plants with 357

loss of ORM function, which leads to increased resistance against P. syringae infection. In 358

addition, our TEM observation gives us another indication of the defense response in plants with 359

decreased ORM1 or ORM2 (Figure 8), showing that active vesicular transport may be caused by 360

16

perturbing the ORM-mediated sphingolipid homeostasis, and this may strengthen cell surface 361

defenses (including formation of cell wall appositions and ROS production on the cell wall). 362

Further, based on the high transcript levels of resistance-related genes (PR1) in plants with loss 363

of ORM function, and especially the up-regulated ER stress-related genes (Liu et al., 2010) and 364

expression of PAD4, SID2, and NPR1 genes related to the SA pathway, we propose that loss of 365

ORM function may affect SA biosynthesis, thereby affecting the plant’s resistance to pathogens. 366

367

368

METHODS 369

Plant Materials and Growth Conditions 370

Wild-type Arabidopsis thaliana (Columbia, Col-0) and T-DNA insertion orm mutants 371

(SALK_046054 and SAIL_1286_D09) from ABRC (http://abrc.osu.edu/) were sown on soil after 372

3 days of stratification at 4°C, followed by cultivation in the greenhouse at 22°C and 50% 373

relative humidity, 16 h light/ 8 h dark with 4800-6000 lux light intensity (PAK bulb, 374

PAK090311). 375

To construct the ORM1 and ORM2 RNAi suppression vectors, the RS300 plasmid was 376

employed to clone an artificial microRNA, as previously described (Schwab et al., 2006). The 377

artificial microRNA was inserted into pCAMBIA1300 and fused with the 35S promoter and 378

NOS terminator. The ORM1 and ORM2 over-expression constructs were generated using 379

pCAMBIA1300 by inserting the open reading frame of ORM1 or ORM2, the 35S promoter, and 380

NOS terminator sequences. Finally, these constructs were transformed into wild type using an 381

Agrobacterium tumefaciens (EHA105)-mediated method. Transformed progenies were screened 382

on 1/2x MS medium containing 0.25 mg/l hygromycin. Homozygous transgenic lines were 383

17

isolated from the T3 generation for further study. All primers used for cloning are shown in 384

Supplemental Table 1. 385

386

Phosphorylation Site Analysis of ORMs 387

For the analysis of potential phosphorylation sites presented in ORM proteins, the amino acid 388

sequences of Arabidopsis ORM1 and ORM2 were submitted to the NetPhos 3.1 389

(http://www.cbs.dtu.dk/services/NetPhos/) and PhosPhAt 4.0 (http://phosphat.uni-390

hohenheim.de/phosphat.html) online tools, respectively (Blom et al., 2004; Durek et al., 2010). 391

392

Quantitative RT-PCR Analysis 393

Total RNA was extracted using the E.Z.N.A. plant RNA kit (R6827-01, Omega Bio-tek). 394

For each sample, 1 μg RNA was reverse transcribed into cDNA using the Primescript RT reagent 395

kit (Takara, DRR047A). Real-time PCR was performed with the SYBR Premix ExTaq kit 396

(Takara, RR820L) according to the manufacturer’s instructions, and quantitatively analyzed with 397

a Step One Plus real-time PCR system (ABI). The 2−△△CT method (Livak and Schmittgen, 2001) 398

was used to determine the relative transcript level of target genes according to the expression 399

level of ACT2 (the internal control). All the experiments were performed in triplicate. The 400

primers used in the present study are listed in Supplemental Table 1. Unless otherwise mentioned, 401

all chemicals were purchased from Sigma (Shanghai, China). 402

403

Subcellular Protein Localization 404

For subcellular protein localization, the 35Spro:GFP:ORM1 and 35Spro:GFP:ORM2 gene 405

expression cassettes were constructed and inserted into pCAMBIA1300. Mesophyll protoplasts 406

were isolated by the tape-Arabidopsis sandwich method and transformed by PEG-calcium 407

18

mediated transfection (Wu et al., 2009). The transfected protoplasts were cultured under dim 408

light (about 300 lux) for 16–24 h at room temperature and observed by confocal microscopy 409

(LSM-780, Carl Zeiss). The excitation/emission wavelengths were: 488 nm/500–530 nm for 410

green fluorescent protein (GFP), 561 nm/580–630 nm for mCherry, and 488 nm/650–750 nm for 411

chlorophyll. 412

413

Sphingolipid Analysis 414

Measurement of sphingolipids was performed and the data were analyzed by Shimadzu 415

UFLC-XR (Shimadzu, Japan) coupled with a hybrid quadrupole time-of-flight mass 416

spectrometer (AB SCIEX Triple TOF 5600+, Foster City, CA, USA) using Phenomenex Luna 417

C8 column (150 mm × 2.0 mm, 3 μm). Briefly, 30 mg of lyophilized sample was homogenized. 418

The internal standards (C17 base D-erythro-sphingosine and d18:1 C12:0-ceramide) were added 419

and extracted with the isopropanol/hexane/water (55:20:25 v/v/v) and incubated at 60°C for 15 420

min. After centrifugation, the supernatants were dried and de-esterified in methylamine in 421

ethanol/water (70:30 v/v) as described previously (Bi et al., 2014; Li et al., 2015; Wu et al., 422

2015). The sphingolipid species were analyzed using the software Multiquant (AB SCIEX). 423

424

Yeast Two-Hybrid Assay 425

Yeast two-hybrid analysis was conducted following the Matchmaker Gold Yeast Two-426

Hybrid System User Manual (Clontech). The full-length open reading frames of ssSPTa and 427

ssSPTb were fused to the bait vector pGBKT7, and the full-length open reading frames of ORM1 428

and ORM2 were cloned into the prey vector pGADT7. Prey and bait vectors were transformed 429

into the yeast strain Y2H Gold (Clontech), and yeast was grown on SD/-Trp-Leu medium for 3 430

19

days. Transformants were incubated at 30°C in a shaking incubator with SD/-Trp-Leu broth until 431

OD600 = 1.0 was obtained, and then tested on selective SD medium at 30°C for 5 days. Empty 432

vectors were used as the negative control. 433

434

Bimolecular Fluorescence Complementation Assay 435

The full-length coding sequences of ORM1 and ORM2 were cloned into pSATN-nEYFP-C1, and 436

full-length coding sequences of ssSPTa and ssSPTb were cloned into pSATN-cYFP-C1 437

(Citovsky et al., 2006). Protoplast isolation and transient expression were performed as described 438

previously (Wu et al., 2009). Empty vectors were co-transformed as negative controls. 439

440

Co-Immunoprecipitation Assay 441

Mesophyll protoplast isolation from 3 to 4-week-old Arabidopsis leaves and DNA transfection 442

were performed as described previously (Wu et al., 2009). For the protocol, 100 μg of prey 443

plasmids and 100 μg of bait plasmids were co-transfected into 1 ml protoplasts (5×105 cells). 444

After expression of proteins for 12 h, protoplasts were pelleted and lysed in 200 μl of 445

immunoprecipitation buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 1 mM EDTA, 10% 446

glycerol, 1% Triton X-100, 13 Roche EDTA-free protease inhibitor cocktail) by vigorous 447

vortexing. For each sample, 20 μl of lysate was saved as the input fraction. The remaining of the 448

lysate was mixed with 300 μl immunoprecipitation buffer and vigorously vortexed. The clear 449

lysate was centrifuged at 16,000 g for 10 min at 4°C, and the supernatant was incubated with 20 450

μl of anti-Flag agarose resins (Sigma) for 4 h at 4°C. The resin was washed three times with 451

immunoprecipitation buffer. The resins were boiled in 40 μl of SDS-PAGE loading buffer to 452

obtain the eluate and prey proteins was detected by immunoblotting analysis using anti-Flag 453

20

antibody and anti-GFP antibody (Cell Signal) at 1:2000 dilution. The immunoblot signal was 454

visualized with the Clarity Western ECL Substrate kit (Bio-Rad). 455

456

H2O2 Detection by CeCl3 Staining and TEM Observation 457

For electron microscopy samples, ~25-day-old Arabidopsis rosette leaves from soil-grown plants 458

were used. The histochemical cerium chloride method was used to detect H2O2 based on 459

generation of cerium hydroxide, as described previously (Bi et al., 2014). The leaves were cut 460

and incubated in 10 mM CeCl3 dissolved in 50 mM MOPS buffer (pH 7.2) for 1 h. Control 461

samples were incubated in MOPS buffer only. Samples were fixed in 2.5% (v/v) glutaraldehyde 462

and 2% (v/v) paraformaldehyde in 0.1 M cacodylate buffer (pH 7.4). Samples were embedded in 463

SPI-PON812 resin (SPI Supplies). Ultrathin sections were obtained on a microtome (Leica EM 464

UC6, Vienna, Austria) and examined without staining. The images were photographed using a 465

transmission electron microscope (JEM-1400, JEOL, Tokyo, Japan) at an accelerating voltage of 466

120 kV. 467

468

Abiotic and Biotic Stress Treatments 469

The seeds of each line were sown on 1/2x MS medium supplemented with FB1 (0.5 μM) or MV 470

(0.5 μM). After 2-3 days at 4°C in the dark, plates were transferred into an incubator with a 16 h 471

light / 8 h dark light regimen. Phenotypes were characterized and scored. For bacterial infection, 472

leaves from 3-week-old plants were injected with the virulent P. syringae strain DG3 at OD600 473

= 0.001 or with 10 mM MgSO4 as a mock-inoculated control. Leaf discs were harvested for 474

21

bacterial quantification at indicated days after inoculation as previous reports (Bi et al., 2014; Wu 475

et al., 2015). 476

477

Accession Numbers 478

Sequence data from this article can be found in the Arabidopsis Genome Initiative or 479

GenBank/EMBL databases under the following accession numbers: ORM1 (At1G01230), ORM2 480

(At5G42000), ssSPTa (At1g06515), ssSPTb (At2g30942), LCB1 (At4g36480), LCB2a 481

(At5g23670), LCB2b (At3g48780), ACT2 (At3g18780), TUBULIN (At5G62690), IRE1a 482

(At2G17520), bZIP28 (At3G10800), bZIP60 (At1G42990), TBF1 (At4G36990), PAD4 483

(At3g52430), SID2 (At1g74710), NPR1 (At1g64280), PR1 (At2g14610), orm1 (SALK_046054), 484

and orm2 (SAIL_1286_D09). 485

486

Supplemental Data 487

Supplemental Figure 1. Sequence alignment of the two Arabidopsis ORM proteins and 488

expression of Arabidopsis ORMs. 489

Supplemental Figure 2. Transmembrane helices predicted in ORM1 and ORM 2. 490

Supplemental Figure 3. Phenotypes and sphingolipid profiles in orm1 and ORM transgenic 491

plants. 492

Supplemental Figure 4. Comparison of major LCB and ceramide components between orm1 493

amiR-ORM2 and wild type. 494

Supplemental Figure 5. Sphingolipid contents in wild type and orm1 amiR-ORM2 plants at 495

different developmental stages. 496

22

Supplemental Figure 6. Subcellular localization of ssSPT and biomolecular fluorescence 497

complementation assay between ORM1 and ssSPTa. 498

Supplemental Figure 7. Subcellular localization of SPT in orm1 amiR-ORM2 plants. 499

Supplemental Table 1. List of primers used in this study. 500

501

ACKNOWLEDGMENTS 502

We thank Edgar Cahoon (University of Nebraska-Lincoln) for helpful discussion and Jian-503

Feng Li (Sun Yat-sen University) for assistance with co-IP experiments. This work was funded 504

by the National Natural Science Foundation of China (31570255), National Key Basic Science 505

973 program (2012CB114006), the Foundation of Guangzhou Science and Technology Project 506

(201504010021) and the Fundamental Research Funds for the Central Universities (16lgjc74) to 507

NY, and China Postdoctoral Science Foundation (2016M592575) to SKS. 508

509

510

Author contributions 511

NY, JL and JXW conceived and designed experiments. JL, JY, CR, KEL, LQH, and HYZ 512

performed the experiments. JL, JY, KEL, JXW, and NY analyzed the data. NY, JL, and SKS 513

wrote the article. 514

515

REFERENCES 516

Berchtold, D., Piccolis, M., Chiaruttini, N., Riezman, I., Riezman, H., Roux, A., Walther, T.C., and 517

Loewith, R. (2012). Plasma membrane stress induces relocalization of Slm proteins and activation of TORC2 518

to promote sphingolipid synthesis. Nat Cell Biol. 14:542-547. 519

23

Bi, F.C., Liu, Z., Wu, J.X., Liang, H., Xi, X.L., Fang, C., Sun, T.J., Yin, J., Dai, G.Y., Rong, 520

C., Greenberg, J.T., Su, W.W., and Yao, N. (2014). Loss of ceramide kinase in Arabidopsis impairs 521

defenses and promotes ceramide accumulation and mitochondrial H2O2 bursts. Plant Cell. 26:3449-3467. 522

Blom, N., Sicheritz-Ponten, T., Gupta, R., Gammeltoft, S. and Brunak, S. (2004). Prediction of post-523

translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics. 4:1633-524

1649. 525

Breslow, D.K., Collins, S.R., Bodenmiller, B., Aebersold, R., Simons, K., Shevchenko, A., Ejsing, 526

C.S., and Weissman, J.S. (2010). Orm family proteins mediate sphingolipid homeostasis. Nature. 463:1048-527

53. 528

Breslow, D.K. (2013). Sphingolipid homeostasis in the endoplasmic reticulum and beyond. Cold Spring Harb 529

Perspect Bio. 5: a013326. 530

Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., and 531

Burtin, P. (2010). Fingolimod (FTY720): discovery and development of an oral drug to treat multiple 532

sclerosis. Nat Rev Drug Discov. 9:883-897. 533

Chen, M., Han, G., Dietrich, C.R., Dunn, T.M., and Cahoon, E.B. (2006). The essential nature of 534

sphingolipids in plants as revealed by the functional identification and characterization of the Arabidopsis 535

LCB1 subunit of serine palmitoyltransferase. Plant Cell. 18:3576-3593. 536

Chen, M., Cahoon, E., Saucedo-García, M., Plasencia, J., and Gavilanes-Ruíz, M. (2009). Plant 537

sphingolipids: structure, synthesis and function. In Lipids in Photosynthesis: Essential and Regulatory 538

Functions, H. Wada and N. Murata, eds. Dordrecht, The Netherlands: Springer, pp. 77–116. 539

Citovsky, V., Lee, L.Y., Vyas, S., Glick, E., Chen, M.H., Vainstein, A., Gafni, Y., Gelvin, S.B., and Tzfira, 540

T. (2006). Subcellular localization of interacting proteins by bimolecular fluorescence complementation in 541

planta. J. Mol. Biol. 362:1120-1131. 542

Dietrich, C.R., Han, G., Chen, M., Berg, R. H., Dunn, T.M., and Cahoon, E.B. (2008). Loss-of-function 543

mutations and inducible RNAi suppression of Arabidopsis LCB2 genes reveal the critical role of sphingolipids 544

in gametophytic and sporophytic cell viability. Plant J. 54:284-298. 545

Durek, P., Schmidt, R., Heazlewood, J.L., Jones, A., MacLean, D., Nagel, A., Kersten, B. and Schulze, 546

W.X. (2010). PhosPhAt: the Arabidopsis thaliana phosphorylation site database. An update. Nucleic Acid Res. 547

38:D828-834. 548

Gable, K., Slife, H., Bacikova, D., Monaghan, E., and Dunn, T.M. (2000). Tsc3p is an 80-amino acid 549

protein associated with serine palmitoyltransferase and required for optimal enzyme activity. J Biol Chem. 550

275:23527-23533. 551

24

Galletti, R., Ferrari, S., and De Lorenzo, G. (2011). Arabidopsis MPK3 and MPK6 play different roles in 552

basal and oligogalacturonide- or flagellin-induced resistance against Botrytis cinerea. Plant Physiol. 157:804-553

814. 554

Gururaj, C., Federman, R., and Chang, A. (2013). Orm proteins integrate multiple signals to maintain 555

sphingolipid homeostasis. J Biol Chem. 288:20453-20463. 556

Han, G., Gupta, S.D., Gable, K., Niranjanakumari, S., Moitra, P., Eichler, F., Brown, R.H. Jr., Harmon, 557

J.M., and Dunn, T.M. (2009). Identification of small subunits of mammalian serine palmitoyltransferase that 558

confer distinct acyl-CoA substrate specificities. Proc Natl Acad Sci. 106:8186–8191. 559

Hannun, Y.A., and Obeid, L.M. (2008). Principles of bioactive lipid signalling: lessons from sphingolipids. 560

Nat. Rev. Mol. Cell Biol. 9:139–150. 561

Han. S., Lone, M.A., Schneiter, R., and Chang, A. (2010). Orm1 and Orm2 are conserved endoplasmic 562

reticulum membrane proteins regulating lipid homeostasis and protein quality control. Proc Natl Acad Sci. 563

107:5851-5856. 564

Hjelmqvist, L., Tuson, M., Marfany, G., Herrero, E., Balcells, S., and Gonzàlez-Duarte, R. (2002). 565

ORMDL proteins are a conserved new family of endoplasmic reticulum membrane protein. Genome Biology 566

3:1-16. 567

Kiefer, K., Carreras-Sureda, A., García-López, R., Rubio-Moscardó, F., Casas, J., Fabriàs, G., and 568

Vicente, R. (2015). Coordinated regulation of the orosomucoid-like gene family expression controls de novo 569

ceramide synthesis in mammalian cells. J Biol Chem. 290:2822-2830. 570

Kimberlin, A.N., Majumder, S., Han, G., Chen, M., Cahoon, R.E., Stone, J.M., Dunn, T.M., and Cahoon, 571

E.B. (2013). Arabidopsis 56–amino acid serine palmitoyltransferase-interacting proteins stimulate sphingolipid 572

synthesis, are essential, and affect mycotoxin sensitivity. Plant Cell. 25:4627–4639. 573

Kimberlin, A.N., Han, G., Chen, M., Cahoon, R.E., Luttgeharm, K.D., Stone, J.M., Markham, J.E., 574

Dunn, T.M. and Cahoon, E.B. (2016). ORM expression alters sphingolipid homeostasis and differentially 575

affects ceramide synthase activities. Plant Physiol. 172:889-900. 576

König, S., Feussner, K., Schwarz, M., Kaever, A., Iven, T., Landesfeind, M., Ternes, P., Karlovsky, 577

P., Lipka, V., and Feussner, I. (2012). Arabidopsis mutants of sphingolipid fatty acid a-hydroxylases 578

accumulate ceramides and salicylates. New Phytol. 196:1086-1097. 579

Lee, Y.J., Huang, X., Kropat, J., Henras, A., Merchant, S.S., Dickson, R.C., and Chanfreau, G.F. (2012). 580

Sphingolipid signaling mediates iron toxicity. Cell Metabolism. 16:90-96. 581

25

Liang, H., Yao, N., Song, J.T., Luo, S., Lu, H., and Greenberg, J.T. (2003). Ceramides modulate 582

programmed cell death in plants. Genes Dev. 17:2636-2641. 583

Li, J., Bi, F.C., Yin, J., Wu, J.X., Rong, C., Wu, J.L., and Yao, N. (2015). An Arabidopsis neutral 584

ceramidase mutant ncer1 accumulates hydroxyceramides and is sensitive to oxidative stress. Front. Plant Sci. 585

6:460. 586

Lingwood, D., and Simons, K. (2010). Lipid rafts as a membrane-organizing principle. Science 327: 46-50. 587

Liu, J.W., and Howell, S.H. (2010). Endoplasmic reticulum protein quality control and its relationship to 588

environmental stress responses in plants. Plant Cell. 22: 2930–2942. 589

Liu, M., Huang, C., Polu, S.R., Schneiter, R., and Chang, A. (2012). Regulation of sphingolipid synthesis 590

through Orm1 and Orm2 in yeast. J Cell Sci. 125:2428-2435. 591

Livak, K.J., and Schmittgen, T.D. (2001). Analysis of relative gene expression data using real-time 592

quantitative PCR and the 2−△△Ct method. Methods. 25:402–408. 593

Markham, J.E., Molino, D., Gissot, L., Bellec, Y., Hématy, K., Marion, J., Belcram, K., Palauqui, J. 594

C., Satiat-Jeunemaître, B., and Faure, J.D. (2011). Sphingolipids containing very-long-chain fatty acids 595

define a secretory pathway for specific polar plasma membrane protein targeting in Arabidopsis. Plant Cell. 23: 596

2362-2378. 597

Modrak, D.E, Gold, D.V., and Glodenberg, D.M. (2006). Sphingolipid targets in cancer therapy. Mol 598

Cancer Ther. 5:200–208. 599

Moffatt, M.F., Kabesch, M., Liang, L., Dixon, A. L., Strachan, D., Heath, S., Depner, M., von Berg, 600

A., Bufe, A., Rietschel, E., et al. (2007). Genetic variants regulating ORMDL3 expression contribute to the 601

risk of childhood asthma. Nature. 448:470-474. 602

Mizuno, S., Ogishima, S., Kitatani, K., Kikuchi, M., Tanaka, H., Yaegashi, N., and Nakaya, J. (2016). 603

Network analysis of a comprehensive knowledge repository reveals a dual role for ceramide in Alzheimer's 604

disease. PLoS ONE. 11: e0148431. 605

Msanne, J., Chen, M., Luttgeharm, K.D., Bradley, A.M., Mays, E. S., Paper, J.M., Boyle, D. L., Cahoon, 606

R.E., Schrick, K., and Cahoon, E.B. (2015). Glucosylceramide is critical for cell-type differentiation and 607

organogenesis, but not for cell viability in Arabidopsis. Plant J. 84: 188-201. 608

Niles, B. J., Mogri, H., Hill, A., Valhakis, A., and Powers, T. (2012). Plasma membrane recruitment and 609

activation of the AGC kinase Ypk1 is mediated by target of rapamycin complex2 (TORC2) and its effector 610

proteins Slm1 and Slm2. Proc Natl Acad Sci.109:1536-1541. 611

26

Okamoto, H., Takuwa, N., Yokomizo, T., Sugimoto, N., Sakurada, S., Shigematsu, H. and Takuwa, Y. 612

(2000). Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-613

coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3. Mol. Cell. Biol. 20: 9247-9261. 614

Park, T.S., Panek, R.L., Rekhter, M.D., Mueller, S.B., Rosebury, W.S., Robertson, A., Hanselman, 615

J.C., Kindt, E., Homan, R., and Karathanasis, S.K. (2006). Modulation of lipoprotein metabolism by 616

inhibition of sphingomyelin synthesis in ApoE knockout mice. Atherosclerosis. 189:264 -272. 617

Peer, M., Stegmann, M., Mueller, M.J., and Waller, F. (2010). Pseudomonas syringae infection triggers de 618

novo synthesis of phytosphingosine from sphinganine in Arabidopsis thaliana. FEBS letters. 84:4053-4056. 619

Roelants, F. M., Breslow, D.K., Muir, A., Weissman, J.S., and Thorner, J. (2011). Protein kinase Ypk1 620

phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces 621

cerevisiae. Proc Natl Acad Sci. 108:19222-19227. 622

Saucedo-García, M., Guevara-García, A., González-Solís, A., Cruz-García, F., Vázquez-Santana, 623

S., Markham, J.E., Lozano-Rosas, M.G., Dietrich, C.R., Ramos-Vega, M., Cahoon, E.B., and Gavilanes-624

Ruíz, M. (2011). MPK6, sphinganine and the LCB2a gene from serine palmitoyltransferase are required in the 625

signaling pathway that mediates cell death induced by long chain bases in Arabidopsis. New Phytol. 191:943-626

957. 627

Schwab, R., Ossowski, S., Riester, M., Warthmann, N., and Weigel, D. (2006). Highly specific gene 628

silencing by artificial microRNAs in Arabidopsis. Plant Cell. 18:1121-1133. 629

Sentelle, R.D., Senkal, C.E., Jiang, W., Ponnusamy, S., Gencer, S., Selvam, S.P., Ramshesh, V. 630

K., Peterson, Y.K., Lemasters, J.J., Szulc, Z. M., Bielawski, J., and Ogretmen, B. (2012). Ceramide targets 631

autophagosomes to mitochondria and induces lethal mitophagy. Nature Chem Biol. 8: 831-838. 632

Shi, C., Yin, J., Liu, Z., Wu, J.X., Zhao, Q., Ren, J., and Yao, N. (2015). A systematic simulation of the 633

effect of salicylic acid on sphingolipid metabolism. Front Plant Sci. 6:186. 634

Shi, L., Bielawski, J., Mu, J., Dong, H., Teng, C., Zhang, J., Yang, X., Tomishige, N., Hanada, 635

K., Hannun, Y.A., and Zuo, J. (2007). Involvement of sphingoid bases in mediating reactive oxygen 636

intermediate production and programmed cell death in Arabidopsis. Cell Research. 17:1030-1040. 637

Shimobayashi, M., Oppliger, W., Moes, S., Jeno, P., and Hall, M.N. (2013). TORC1-regulated protein 638

kinase Npr1 phosphorlates Orm to stimulate complex sphingolipid synthesis. Mol Biol Cell. 24:870-881. 639

Siow, D.L., and Wattenberg, B.W. (2012). Mammalian ORMDL proteins mediate the feedback response in 640

ceramide biosynthesis. J Biol Chem. 287:40198-40204. 641

27

Summers, S.A., and Nelson, D.H. (2005). A role for sphingolipids in producing the common features of type 642

2 diabetes, metabolic syndrome X, and Cushing's syndrome. Diabetes. 54: 591–602. 643

Sun, Y., Miao, Y., Yamane, Y., Zhang, C., Shokat, K. M., Takematsu, H., Kozutsumi, Y., Drubin, D.G. 644

(2012). Orm protein phosphoregulation mediates transient sphingolipid biosynthesis response to heat stress via 645

Pkh-Ypk and Cdc55-PP2A pathways. Mol Biol Cell. 23:2388-2398. 646

Tafesse, F.G, and Hoithuis, J.C.M. (2010). A brake on lipid synthesis. Nature. 463:1028-1029. 647

Teng, C., Dong, H., Shi, L., Deng, Y., Mu, J., Zhang, J., Yang, X., and Zuo, J. (2008). Serine 648

palmitoyltransferase, a key enzyme for de novo synthesis of sphingolipids, is essential for male gametophyte 649

development in Arabidopsis. Plant Physiol.146:1322-1332. 650

Ternes, P., Feussner, K., Werner, S., Lerche, J., Iven, T., Heilmann, I., Riezman, H., and Feussner, I. 651

(2011). Disruption of the ceramide synthase LOH1 causes spontaneous cell death in Arabidopsis thaliana. New 652

Phytol. 192:841-854. 653

Wang, W., Yang, X., Tangchaiburana, S., Ndeh, R., Markham, J. E., Tsegaye, Y., Dunn, T. M., Wang, 654

G.L., Bellizzi, M., Parsons, J.F., Morrissey, D., Bravo, J.E., Lynch, D.V., and Xiao, S. (2008). An 655

inositolphosphorylceramide synthase is involved in regulation of plant programmed cell death associated with 656

defense in Arabidopsis. Plant Cell. 20: 3163–3179. 657

Wu, F.H., Shen, S.C., Lee, L.Y., Lee, S.H., Chan, M.T., and Lin, C.S. (2009). Tape-Arabidopsis Sandwich 658

- a simpler Arabidopsis protoplast isolation method. Plant Methods. 5:16. 659

Wu, J.X., Li, J., Liu, Z., Yin, J., Chang, Z.Y., Rong, C., Wu, J.L., Bi, F.C., and Yao, N. (2015). The 660

Arabidopsis ceramidase AtACER functions in disease resistance and salt tolerance. Plant J. 81:767–780. 661

Zhang, H., Huang, L., Li, X.H., Ouyang, Z.G., Yu, Y. M., Li, D.Y., and Song, F.M. (2013).Overexpression 662

of a rice long-chain base kinase gene OsLCBK1 in tobacco improves oxidative stress tolerance. Plant Biotech. 663

30:9-16. 664

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Figure legends 666

667

Figure 1. Loss-of-function of ORM1 and ORM2 causes an early-senescence phenotype and 668

sphingolipid accumulation. 669

(A) The structures of Arabidopsis ORM1 and ORM2 and the locations of T-DNA insertions. 670

(B and C) The phenotype of wild-type and ORM loss-of-function plants at 26 (B) and 35 (C) 671

days old. The white arrows indicate leaf senescence in orm1 amiR-ORM2 plants. 672

(D) Subcellular localization of ORM proteins. The fusion constructs 35Spro:GFP-ORM1 and 673

35Spro:GFP-ORM2 were co-expressed with the ER mCherry marker (TAIR, CD3-960) by 674

transient expression in protoplasts. The 35Spro:GFP construct and CD3-960 were co-transformed 675

as controls. The images were obtained by confocal microscopy after 16 h incubation. The 676

experiments were repeated at least 3 times with similar results. Bars = 5 μm. 677

(E) Sphingolipids accumulated in orm1 amiR-ORM2 plants. Sphingolipids were extracted from 678

28-day-old plants following the steps described in Methods. The main sphingolipids were 679

separated and identified by HPLC-ESI-MS. The amount of total long-chain bases (LCB), 680

ceramides (Cer), hydroxyceramides (hCer) and glucosylceramides (gCer) were quantified (see 681

Supplemental Figure 4 for major LCB and ceramide species). The experiment was repeated three 682

times with similar results using independent samples. Values are means ±SE from three technical 683

replicates. Asterisks show a significant difference from the wild type using Student’s t-test (*** 684

p < 0.001). 685

686

Figure 2. ORM suppresses the de novo biosynthesis of sphingolipids in Arabidopsis. 687

29

Seven-day-old wild-type (WT), orm1, amiR-ORM2, and orm1 amiR-ORM2 seedlings were 688

transferred to 5 mM 15N-serine labeled N-deficient 1/2x MS liquid medium for 9-24 h. 689

Sphingolipids were then extracted and measured as described in Methods. Note that except total 690

LCB and total ceramides (top panels), major LCB and ceramide species significantly increased at 691

24 h in orm1 amiR-ORM2 seedlings. Error bars represent the means ±SE from triplicate 692

biological repeats. Asterisks show a significant difference from the wild type using Student’s t-693

test (*p < 0.05, **p < 0.01, *** p < 0.001). 694

695

Figure 3. Physical interaction between ORM and ssSPT. 696

(A) Yeast two-hybrid assay showing that ssSPTa and ssSPTb interact with ORM1 and ORM2. 697

Vectors pGADT7 (AD) and pGBKT7 (BD) were used as negative controls. 698

(B) Coimmunoprecipitation assays of ORM1, ORM2, and ssSPTa, ssSPTb in protoplasts. Flag-699

tagged ORM1 and ORM2 were immunoprecipitated with an anti-Flag antibody, and 700

coimmunoprecipitated ssSPTa-GFP and ssSPTb-GFP were detected by an anti-GFP antibody. 701

“+” or “-”denote the presence or absence of the protein in each sample. Free GFP was used as a 702

negative control. 703

(C) BiFC interaction of ssSPTa and ORM1, ssSPTb and ORM2, ssSPTa and ORM2, ssSPTb and 704

ORM2 in Arabidopsis leaf protoplasts. Overlaid images show signals for YFP (yellow) and 705

chloroplasts (blue). Empty vectors were used as negative controls. Scale bars = 5 μm. 706

707

Figure 4. Phenotypes of wild-type and ORM transgenic seedlings after FB1 treatments. 708

Seedlings of wild-type, orm1, amiR-ORM2, and orm1 amiR-ORM2 plants and overexpression 709

lines (ORM1-OX, ORM2-OX) were grown on 1/2x MS with or without 0.5 μM FB1 for 9 days 710

30

and then photographed. Percentage of seedling mortality after 0.5 μM FB1 treatment is shown in 711

the right panel. Asterisks show a significant difference from the wild type using Student’s t-test 712

(*p < 0.05, **p < 0.01, *** p < 0.001). 713

714

Figure 5. Ultrastructural features of orm1 amiR-ORM2 leaves. 715

(A-E) Representative TEM images of ultrastructure of 25-day-old wild-type (A) and orm1 amiR-716

ORM2 (B-E) leaves. Note an aggregate of condensed chromatin (B, a white arrow), abnormal ER 717

with loose structure (C), many small bubbles (C and D, white stars) around the plasma 718

membrane and cell wall and a large cell wall apposition in the orm1 amiR-ORM2 leaf cell (E). 719

(F-K) H2O2 production in wild-type (F) and orm1 amiR-ORM2 (G-K) leaves observed by TEM 720

using the histochemical cerium chloride method. (F) No cerium deposits were observed in the 721

representative wild-type control cell. (G and H) Cerium deposits in the plasma membrane and 722

cell wall (black arrows). Note vesicular bodies with double membrane (black arrowheads). (I) 723

Cerium deposits around the ER close to the cell wall. (J and K) H2O2 inside mitochondria (J, 724

white arrowheads) and irregular vacuolization (K). 725

Ch, chloroplast; CW, cell wall; CWA, cell wall apposition; ER, endoplasmic reticulum; G, Golgi; 726

M, mitochondrion; N, nucleus; S, starch grain. Bars = 500 nm. 727

728

Figure 6. Expression of genes related to ER stress and defense in orm1 amiR-ORM2 plants. 729

Approximately 26-day-old wild-type, orm1, amiR-ORM2, and orm1 amiR-ORM2 plants were 730

used to monitor the expression of indicated genes by RT-qPCR. IRE1a (At2G17520), bZIP28 731

(At3G10800), bZIP60 (At1G42990), TBF1 (At4G36990), PR1 (At2g14610), PAD4 (At3g52430), 732

SID2 (At1g74710), and NPR1 (At1g64280) were used for analysis. ACT2 transcript levels were 733

31

used as the internal control. (A) ER stress-related genes. (B) Salicylic acid pathway-related genes. 734

Gene expression values are presented relative to average wild-type levels (set to 1). Samples 735

were analyzed in triplicate biological repeats with similar results. Bars indicate ±SE from three 736

technical replicates. Different letters represent a significant difference from the wild type using a 737

post hoc multiple t-test (p<0.001). 738

739

Figure 7. Loss of ORM protein enhances the resistance to abiotic stress and biotic stress. 740

(A) The phenotype of wild-type and mutant seedlings after MV treatments. Seedlings were 741

grown on 1/2x MS with or without 0.5 μM MV for 7 days and then photographed. The white 742

square indicates one seedling with a severe phenotype. 743

(B) Percentage of seedlings with a severe phenotype after 0.5 μM MV treatments. At least 350 744

seedlings were counted in each genotype. Values represent means ± SE from two independent 745

experiments. 746

(C) Cell death symptom after infection by P. syringae virulent strain DG3 at OD600 = 0.005 for 747

3 days. MgSO4 as a mock-inoculated control was used. 748

(D) Growth of P. syringae virulent strain DG3 in wild-type and orm1 amiR-ORM2 plants after 749

infection at OD600 = 0.001. Lesion-free plants were inoculated with bacteria at 3 weeks of age. 750

The mean value of the growth of bacteria in nine leaves is indicated in each case. Bars indicate 751

standard deviations. This experiment was repeated three times with similar results. Asterisks 752

show a significant difference from the wild type using Student’s t-test (*p < 0.05). 753

754

Figure 8. Model of ORM1 and ORM2-mediated sphingolipid homeostasis and plant resistance. 755

32

The proposed model for ORM1 and ORM2 functions as negative regulators of de novo 756

sphingolipid synthesis in Arabidopsis based on the current study. Serine palmitoyltransferase 757

(SPT), localized on the ER, consists of LCB1, LCB2a/b, and ssSPTa/b and catalyzes the first 758

step in sphingolipid biosynthesis. SPT demonstrates extremely low enzyme activity without 759

ssSPTa/b (Kimberlin et al., 2013). We found that ORM1 and ORM2 inhibit the biosynthesis of 760

LCB through physically interacting with ssSPTa/b. Moreover, in plants lacking ORM1 or ORM2, 761

the profile of sphingolipids was enhanced, accompanied by a senescence phenotype and 762

increased disease resistance. A possible mechanism related to defense in ORM1 and ORM2 loss-763

of-function plants is proposed. LCB, long chain base; ER, endoplasmic reticulum; CW, cell wall; 764

SA, salicylic acid; ROS, reactive oxygen species; CWA, cell wall apposition. Red letters and 765

arrows represent data in this study. The black dotted arrow represents our speculation. 766

767

Parsed CitationsBerchtold, D., Piccolis, M., Chiaruttini, N., Riezman, I., Riezman, H., Roux, A., Walther, T.C., and Loewith, R. (2012). Plasmamembrane stress induces relocalization of Slm proteins and activation of TORC2 to promote sphingolipid synthesis. Nat Cell Biol.14:542-547.

Pubmed: Author and TitleCrossRef: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Bi, F.C., Liu, Z., Wu, J.X., Liang, H., Xi, X.L., Fang, C., Sun, T.J., Yin, J., Dai, G.Y., Rong, C., Greenberg, J.T., Su, W.W., and Yao, N.(2014). Loss of ceramide kinase in Arabidopsis impairs defenses and promotes ceramide accumulation and mitochondrial H2O2bursts. Plant Cell. 26:3449-3467.


Blom, N., Sicheritz-Ponten, T., Gupta, R., Gammeltoft, S. and Brunak, S. (2004). Prediction of post-translational glycosylation andphosphorylation of proteins from the amino acid sequence. Proteomics. 4:1633-1649.


Breslow, D.K., Collins, S.R., Bodenmiller, B., Aebersold, R., Simons, K., Shevchenko, A., Ejsing, C.S., and Weissman, J.S. (2010).Orm family proteins mediate sphingolipid homeostasis. Nature. 463:1048-53.


Breslow, D.K. (2013). Sphingolipid homeostasis in the endoplasmic reticulum and beyond. Cold Spring Harb Perspect Bio. 5:a013326.


Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., and Burtin, P. (2010). Fingolimod(FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 9:883-897.


Chen, M., Han, G., Dietrich, C.R., Dunn, T.M., and Cahoon, E.B. (2006). The essential nature of sphingolipids in plants as revealedby the functional identification and characterization of the Arabidopsis LCB1 subunit of serine palmitoyltransferase. Plant Cell.18:3576-3593.


Chen, M., Cahoon, E., Saucedo-García, M., Plasencia, J., and Gavilanes-Ruíz, M. (2009). Plant sphingolipids: structure, synthesisand function. In Lipids in Photosynthesis: Essential and Regulatory Functions, H. Wada and N. Murata, eds. Dordrecht, TheNetherlands: Springer, pp. 77-116.


Citovsky, V., Lee, L.Y., Vyas, S., Glick, E., Chen, M.H., Vainstein, A., Gafni, Y., Gelvin, S.B., and Tzfira, T. (2006). Subcellularlocalization of interacting proteins by bimolecular fluorescence complementation in planta. J. Mol. Biol. 362:1120-1131.


Dietrich, C.R., Han, G., Chen, M., Berg, R. H., Dunn, T.M., and Cahoon, E.B. (2008). Loss-of-function mutations and inducible RNAisuppression of Arabidopsis LCB2 genes reveal the critical role of sphingolipids in gametophytic and sporophytic cell viability.Plant J. 54:284-298.


Durek, P., Schmidt, R., Heazlewood, J.L., Jones, A., MacLean, D., Nagel, A., Kersten, B. and Schulze, W.X. (2010). PhosPhAt: theArabidopsis thaliana phosphorylation site database. An update. Nucleic Acid Res. 38:D828-834.


Gable, K., Slife, H., Bacikova, D., Monaghan, E., and Dunn, T.M. (2000). Tsc3p is an 80-amino acid protein associated with serinepalmitoyltransferase and required for optimal enzyme activity. J Biol Chem. 275:23527-23533.


http://www.ncbi.nlm.nih.gov/pubmed?term=Berchtold%2C D%2E%2C Piccolis%2C M%2E%2C Chiaruttini%2C N%2E%2C Riezman%2C I%2E%2C Riezman%2C H%2E%2C Roux%2C A%2E%2C Walther%2C T%2EC%2E%2C and Loewith%2C R%2E %282012%29%2E Plasma membrane stress induces relocalization of Slm proteins and activation of TORC2 to promote sphingolipid synthesis%2E Nat Cell Biol%2E 14%3A542%2D547%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Berchtold, D., Piccolis, M., Chiaruttini, N., Riezman, I., Riezman, H., Roux, A., Walther, T.C., and Loewith, R. (2012). Plasma membrane stress induces relocalization of Slm proteins and activation of TORC2 to promote sphingolipid synthesis. Nat Cell Biol. 14:542-547.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Berchtold,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Plasma membrane stress induces relocalization of Slm proteins and activation of TORC2 to promote sphingolipid synthesis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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http://search.crossref.org/?page=1&rows=2&q=Bi, F.C., Liu, Z., Wu, J.X., Liang, H., Xi, X.L., Fang, C., Sun, T.J., Yin, J., Dai, G.Y., Rong, C., Greenberg, J.T., Su, W.W., and Yao, N. (2014). Loss of ceramide kinase in Arabidopsis impairs defenses and promotes ceramide accumulation and mitochondrial H2O2 bursts. Plant Cell. 26:3449-3467.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Bi,&hl=en&c2coff=1

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http://www.ncbi.nlm.nih.gov/pubmed?term=Blom%2C N%2E%2C Sicheritz%2DPonten%2C T%2E%2C Gupta%2C R%2E%2C Gammeltoft%2C S%2E and Brunak%2C S%2E %282004%29%2E Prediction of post%2Dtranslational glycosylation and phosphorylation of proteins from the amino acid sequence%2E Proteomics%2E 4%3A1633%2D1649%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Blom, N., Sicheritz-Ponten, T., Gupta, R., Gammeltoft, S. and Brunak, S. (2004). Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics. 4:1633-1649.

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http://search.crossref.org/?page=1&rows=2&q=Breslow, D.K., Collins, S.R., Bodenmiller, B., Aebersold, R., Simons, K., Shevchenko, A., Ejsing, C.S., and Weissman, J.S. (2010). Orm family proteins mediate sphingolipid homeostasis. Nature. 463:1048-53.

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http://scholar.google.com/scholar?as_q=Orm family proteins mediate sphingolipid homeostasis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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http://www.ncbi.nlm.nih.gov/pubmed?term=Breslow%2C D%2EK%2E %282013%29%2E Sphingolipid homeostasis in the endoplasmic reticulum and beyond%2E Cold Spring Harb Perspect Bio%2E 5%3A a013326%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Breslow, D.K. (2013). Sphingolipid homeostasis in the endoplasmic reticulum and beyond. Cold Spring Harb Perspect Bio. 5: a013326.

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http://www.ncbi.nlm.nih.gov/pubmed?term=Brinkmann%2C V%2E%2C Billich%2C A%2E%2C Baumruker%2C T%2E%2C Heining%2C P%2E%2C Schmouder%2C R%2E%2C Francis%2C G%2E%2C Aradhye%2C S%2E%2C and Burtin%2C P%2E %282010%29%2E Fingolimod %28FTY720%29%3A discovery and development of an oral drug to treat multiple sclerosis%2E Nat Rev Drug Discov%2E 9%3A883%2D897%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., and Burtin, P. (2010). Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 9:883-897.

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http://scholar.google.com/scholar?as_q=Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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http://search.crossref.org/?page=1&rows=2&q=Chen, M., Cahoon, E., Saucedo-Garc�a, M., Plasencia, J., and Gavilanes-Ru�z, M. (2009). Plant sphingolipids: structure, synthesis and function. In Lipids in Photosynthesis: Essential and Regulatory Functions, H. Wada and N. Murata, eds. Dordrecht, The Netherlands: Springer, pp. 77-116.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Chen,&hl=en&c2coff=1

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http://search.crossref.org/?page=1&rows=2&q=Citovsky, V., Lee, L.Y., Vyas, S., Glick, E., Chen, M.H., Vainstein, A., Gafni, Y., Gelvin, S.B., and Tzfira, T. (2006). Subcellular localization of interacting proteins by bimolecular fluorescence complementation in planta. J. Mol. Biol. 362:1120-1131.

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http://scholar.google.com/scholar?as_q=Subcellular localization of interacting proteins by bimolecular fluorescence complementation in planta&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Subcellular localization of interacting proteins by bimolecular fluorescence complementation in planta&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Citovsky,&as_ylo=2006&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Dietrich%2C C%2ER%2E%2C Han%2C G%2E%2C Chen%2C M%2E%2C Berg%2C R%2E H%2E%2C Dunn%2C T%2EM%2E%2C and Cahoon%2C E%2EB%2E %282008%29%2E Loss%2Dof%2Dfunction mutations and inducible RNAi suppression of Arabidopsis LCB2 genes reveal the critical role of sphingolipids in gametophytic and sporophytic cell viability%2E Plant J%2E 54%3A284%2D298%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Dietrich, C.R., Han, G., Chen, M., Berg, R. H., Dunn, T.M., and Cahoon, E.B. (2008). Loss-of-function mutations and inducible RNAi suppression of Arabidopsis LCB2 genes reveal the critical role of sphingolipids in gametophytic and sporophytic cell viability. Plant J. 54:284-298.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Dietrich,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Loss-of-function mutations and inducible RNAi suppression of Arabidopsis LCB2 genes reveal the critical role of sphingolipids in gametophytic and sporophytic cell viability&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Loss-of-function mutations and inducible RNAi suppression of Arabidopsis LCB2 genes reveal the critical role of sphingolipids in gametophytic and sporophytic cell viability&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Dietrich,&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Durek%2C P%2E%2C Schmidt%2C R%2E%2C Heazlewood%2C J%2EL%2E%2C Jones%2C A%2E%2C MacLean%2C D%2E%2C Nagel%2C A%2E%2C Kersten%2C B%2E and Schulze%2C W%2EX%2E %282010%29%2E PhosPhAt%3A the Arabidopsis thaliana phosphorylation site database%2E An update%2E Nucleic Acid Res%2E 38%3AD828%2D834%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Durek, P., Schmidt, R., Heazlewood, J.L., Jones, A., MacLean, D., Nagel, A., Kersten, B. and Schulze, W.X. (2010). PhosPhAt: the Arabidopsis thaliana phosphorylation site database. An update. Nucleic Acid Res. 38:D828-834.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Durek,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=PhosPhAt: the Arabidopsis thaliana phosphorylation site database&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=PhosPhAt: the Arabidopsis thaliana phosphorylation site database&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Durek,&as_ylo=2010&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Gable%2C K%2E%2C Slife%2C H%2E%2C Bacikova%2C D%2E%2C Monaghan%2C E%2E%2C and Dunn%2C T%2EM%2E %282000%29%2E Tsc3p is an 80%2Damino acid protein associated with serine palmitoyltransferase and required for optimal enzyme activity%2E J Biol Chem%2E 275%3A23527%2D23533%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Gable, K., Slife, H., Bacikova, D., Monaghan, E., and Dunn, T.M. (2000). Tsc3p is an 80-amino acid protein associated with serine palmitoyltransferase and required for optimal enzyme activity. J Biol Chem. 275:23527-23533.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Gable,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Tsc3p is an 80-amino acid protein associated with serine palmitoyltransferase and required for optimal enzyme activity&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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Galletti, R., Ferrari, S., and De Lorenzo, G. (2011). Arabidopsis MPK3 and MPK6 play different roles in basal andoligogalacturonide- or flagellin-induced resistance against Botrytis cinerea. Plant Physiol. 157:804-814.


Gururaj, C., Federman, R., and Chang, A. (2013). Orm proteins integrate multiple signals to maintain sphingolipid homeostasis. JBiol Chem. 288:20453-20463.


Han, G., Gupta, S.D., Gable, K., Niranjanakumari, S., Moitra, P., Eichler, F., Brown, R.H. Jr., Harmon, J.M., and Dunn, T.M. (2009).Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities. ProcNatl Acad Sci. 106:8186-8191.


Hannun, Y.A., and Obeid, L.M. (2008). Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell Biol.9:139-150.


Han. S., Lone, M.A., Schneiter, R., and Chang, A. (2010). Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteinsregulating lipid homeostasis and protein quality control. Proc Natl Acad Sci. 107:5851-5856.


Hjelmqvist, L., Tuson, M., Marfany, G., Herrero, E., Balcells, S., and Gonzàlez-Duarte, R. (2002). ORMDL proteins are a conservednew family of endoplasmic reticulum membrane protein. Genome Biology 3:1-16.


Kiefer, K., Carreras-Sureda, A., García-López, R., Rubio-Moscardó, F., Casas, J., Fabriàs, G., and Vicente, R. (2015). Coordinatedregulation of the orosomucoid-like gene family expression controls de novo ceramide synthesis in mammalian cells. J Biol Chem.290:2822-2830.


Kimberlin, A.N., Majumder, S., Han, G., Chen, M., Cahoon, R.E., Stone, J.M., Dunn, T.M., and Cahoon, E.B. (2013). Arabidopsis 56-amino acid serine palmitoyltransferase-interacting proteins stimulate sphingolipid synthesis, are essential, and affect mycotoxinsensitivity. Plant Cell. 25:4627-4639.


Kimberlin, A.N., Han, G., Chen, M., Cahoon, R.E., Luttgeharm, K.D., Stone, J.M., Markham, J.E., Dunn, T.M. and Cahoon, E.B. (2016).ORM expression alters sphingolipid homeostasis and differentially affects ceramide synthase activities. Plant Physiol. 172:889-900.


König, S., Feussner, K., Schwarz, M., Kaever, A., Iven, T., Landesfeind, M., Ternes, P., Karlovsky, P., Lipka, V., and Feussner, I.(2012). Arabidopsis mutants of sphingolipid fatty acid a-hydroxylases accumulate ceramides and salicylates. New Phytol. 196:1086-1097.


Lee, Y.J., Huang, X., Kropat, J., Henras, A., Merchant, S.S., Dickson, R.C., and Chanfreau, G.F. (2012). Sphingolipid signalingmediates iron toxicity. Cell Metabolism. 16:90-96.


Liang, H., Yao, N., Song, J.T., Luo, S., Lu, H., and Greenberg, J.T. (2003). Ceramides modulate programmed cell death in plants.Genes Dev. 17:2636-2641.


Li, J., Bi, F.C., Yin, J., Wu, J.X., Rong, C., Wu, J.L., and Yao, N. (2015). An Arabidopsis neutral ceramidase mutant ncer1 accumulateshydroxyceramides and is sensitive to oxidative stress. Front. Plant Sci. 6:460.

Pubmed: Author and TitleCrossRef: Author and Title

http://www.ncbi.nlm.nih.gov/pubmed?term=Galletti%2C R%2E%2C Ferrari%2C S%2E%2C and De Lorenzo%2C G%2E %282011%29%2E Arabidopsis MPK3 and MPK6 play different roles in basal and oligogalacturonide%2D or flagellin%2Dinduced resistance against Botrytis cinerea%2E Plant Physiol%2E 157%3A804%2D814%2E&dopt=abstract

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http://www.ncbi.nlm.nih.gov/pubmed?term=K�nig%2C S%2E%2C Feussner%2C K%2E%2C Schwarz%2C M%2E%2C Kaever%2C A%2E%2C Iven%2C T%2E%2C Landesfeind%2C M%2E%2C Ternes%2C P%2E%2C Karlovsky%2C P%2E%2C Lipka%2C V%2E%2C and Feussner%2C I%2E %282012%29%2E Arabidopsis mutants of sphingolipid fatty acid a%2Dhydroxylases accumulate ceramides and salicylates%2E New Phytol%2E 196%3A1086%2D1097%2E&dopt=abstract

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http://scholar.google.com/scholar?as_q=Sphingolipid signaling mediates iron toxicity&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Sphingolipid signaling mediates iron toxicity&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Lee,&as_ylo=2012&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Liang%2C H%2E%2C Yao%2C N%2E%2C Song%2C J%2ET%2E%2C Luo%2C S%2E%2C Lu%2C H%2E%2C and Greenberg%2C J%2ET%2E %282003%29%2E Ceramides modulate programmed cell death in plants%2E Genes Dev%2E 17%3A2636%2D2641%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Liang, H., Yao, N., Song, J.T., Luo, S., Lu, H., and Greenberg, J.T. (2003). Ceramides modulate programmed cell death in plants. Genes Dev. 17:2636-2641.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Liang,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Ceramides modulate programmed cell death in plants&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Ceramides modulate programmed cell death in plants&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Liang,&as_ylo=2003&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Li%2C J%2E%2C Bi%2C F%2EC%2E%2C Yin%2C J%2E%2C Wu%2C J%2EX%2E%2C Rong%2C C%2E%2C Wu%2C J%2EL%2E%2C and Yao%2C N%2E %282015%29%2E An Arabidopsis neutral ceramidase mutant ncer1 accumulates hydroxyceramides and is sensitive to oxidative stress%2E Front%2E Plant Sci%2E 6%3A460%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Li, J., Bi, F.C., Yin, J., Wu, J.X., Rong, C., Wu, J.L., and Yao, N. (2015). An Arabidopsis neutral ceramidase mutant ncer1 accumulates hydroxyceramides and is sensitive to oxidative stress. Front. Plant Sci. 6:460.

Google Scholar: Author Only Title Only Author and Title

Lingwood, D., and Simons, K. (2010). Lipid rafts as a membrane-organizing principle. Science 327: 46-50.Pubmed: Author and TitleCrossRef: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Liu, J.W., and Howell, S.H. (2010). Endoplasmic reticulum protein quality control and its relationship to environmental stressresponses in plants. Plant Cell. 22: 2930-2942.


Liu, M., Huang, C., Polu, S.R., Schneiter, R., and Chang, A. (2012). Regulation of sphingolipid synthesis through Orm1 and Orm2 inyeast. J Cell Sci. 125:2428-2435.


Livak, K.J., and Schmittgen, T.D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-??Ctmethod. Methods. 25:402-408.


Markham, J.E., Molino, D., Gissot, L., Bellec, Y., Hématy, K., Marion, J., Belcram, K., Palauqui, J. C., Satiat-Jeunemaître, B., andFaure, J.D. (2011). Sphingolipids containing very-long-chain fatty acids define a secretory pathway for specific polar plasmamembrane protein targeting in Arabidopsis. Plant Cell. 23: 2362-2378.


Modrak, D.E, Gold, D.V., and Glodenberg, D.M. (2006). Sphingolipid targets in cancer therapy. Mol Cancer Ther. 5:200-208.Pubmed: Author and TitleCrossRef: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Moffatt, M.F., Kabesch, M., Liang, L., Dixon, A. L., Strachan, D., Heath, S., Depner, M., von Berg, A., Bufe, A., Rietschel, E., et al.(2007). Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 448:470-474.


Mizuno, S., Ogishima, S., Kitatani, K., Kikuchi, M., Tanaka, H., Yaegashi, N., and Nakaya, J. (2016). Network analysis of acomprehensive knowledge repository reveals a dual role for ceramide in Alzheimer's disease. PLoS ONE. 11: e0148431.


Msanne, J., Chen, M., Luttgeharm, K.D., Bradley, A.M., Mays, E. S., Paper, J.M., Boyle, D. L., Cahoon, R.E., Schrick, K., and Cahoon,E.B. (2015). Glucosylceramide is critical for cell-type differentiation and organogenesis, but not for cell viability in Arabidopsis.Plant J. 84: 188-201.


Niles, B. J., Mogri, H., Hill, A., Valhakis, A., and Powers, T. (2012). Plasma membrane recruitment and activation of the AGC kinaseYpk1 is mediated by target of rapamycin complex2 (TORC2) and its effector proteins Slm1 and Slm2. Proc Natl Acad Sci.109:1536-1541.


Okamoto, H., Takuwa, N., Yokomizo, T., Sugimoto, N., Sakurada, S., Shigematsu, H. and Takuwa, Y. (2000). Inhibitory regulation ofRac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but notEDG1 or EDG3. Mol. Cell. Biol. 20: 9247-9261.


Park, T.S., Panek, R.L., Rekhter, M.D., Mueller, S.B., Rosebury, W.S., Robertson, A., Hanselman, J.C., Kindt, E., Homan, R., andKarathanasis, S.K. (2006). Modulation of lipoprotein metabolism by inhibition of sphingomyelin synthesis in ApoE knockout mice.Atherosclerosis. 189:264 -272.


Peer, M., Stegmann, M., Mueller, M.J., and Waller, F. (2010). Pseudomonas syringae infection triggers de novo synthesis ofphytosphingosine from sphinganine in Arabidopsis thaliana. FEBS letters. 84:4053-4056.

Pubmed: Author and Title

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Li,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=An Arabidopsis neutral ceramidase mutant ncer1 accumulates hydroxyceramides and is sensitive to oxidative stress&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=An Arabidopsis neutral ceramidase mutant ncer1 accumulates hydroxyceramides and is sensitive to oxidative stress&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Li,&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Lingwood%2C D%2E%2C and Simons%2C K%2E %282010%29%2E Lipid rafts as a membrane%2Dorganizing principle%2E Science 327%3A 46%2D50%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Lingwood, D., and Simons, K. (2010). Lipid rafts as a membrane-organizing principle. Science 327: 46-50.

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http://www.ncbi.nlm.nih.gov/pubmed?term=Liu%2C J%2EW%2E%2C and Howell%2C S%2EH%2E %282010%29%2E Endoplasmic reticulum protein quality control and its relationship to environmental stress responses in plants%2E Plant Cell%2E 22%3A 2930%2D2942%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Liu, J.W., and Howell, S.H. (2010). Endoplasmic reticulum protein quality control and its relationship to environmental stress responses in plants. Plant Cell. 22: 2930-2942.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Liu,&hl=en&c2coff=1

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http://search.crossref.org/?page=1&rows=2&q=Liu, M., Huang, C., Polu, S.R., Schneiter, R., and Chang, A. (2012). Regulation of sphingolipid synthesis through Orm1 and Orm2 in yeast. J Cell Sci. 125:2428-2435.

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http://www.ncbi.nlm.nih.gov/pubmed?term=Livak%2C K%2EJ%2E%2C and Schmittgen%2C T%2ED%2E %282001%29%2E Analysis of relative gene expression data using real%2Dtime quantitative PCR and the 2%2D%3F%3FCt method%2E Methods%2E 25%3A402%2D408%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Livak, K.J., and Schmittgen, T.D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-??Ct method. Methods. 25:402-408.

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http://www.ncbi.nlm.nih.gov/pubmed?term=Markham%2C J%2EE%2E%2C Molino%2C D%2E%2C Gissot%2C L%2E%2C Bellec%2C Y%2E%2C H�maty%2C K%2E%2C Marion%2C J%2E%2C Belcram%2C K%2E%2C Palauqui%2C J%2E C%2E%2C Satiat%2DJeunema�tre%2C B%2E%2C and Faure%2C J%2ED%2E %282011%29%2E Sphingolipids containing very%2Dlong%2Dchain fatty acids define a secretory pathway for specific polar plasma membrane protein targeting in Arabidopsis%2E Plant Cell%2E 23%3A 2362%2D2378%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Markham, J.E., Molino, D., Gissot, L., Bellec, Y., H�maty, K., Marion, J., Belcram, K., Palauqui, J. C., Satiat-Jeunema�tre, B., and Faure, J.D. (2011). Sphingolipids containing very-long-chain fatty acids define a secretory pathway for specific polar plasma membrane protein targeting in Arabidopsis. Plant Cell. 23: 2362-2378.

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http://www.ncbi.nlm.nih.gov/pubmed?term=Modrak%2C D%2EE%2C Gold%2C D%2EV%2E%2C and Glodenberg%2C D%2EM%2E %282006%29%2E Sphingolipid targets in cancer therapy%2E Mol Cancer Ther%2E 5%3A200%2D208%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Modrak, D.E, Gold, D.V., and Glodenberg, D.M. (2006). Sphingolipid targets in cancer therapy. Mol Cancer Ther. 5:200-208.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Modrak,&hl=en&c2coff=1

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http://www.ncbi.nlm.nih.gov/pubmed?term=Moffatt%2C M%2EF%2E%2C Kabesch%2C M%2E%2C Liang%2C L%2E%2C Dixon%2C A%2E L%2E%2C Strachan%2C D%2E%2C Heath%2C S%2E%2C Depner%2C M%2E%2C von Berg%2C A%2E%2C Bufe%2C A%2E%2C Rietschel%2C E%2E%2C et al%2E %282007%29%2E Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma%2E Nature%2E 448%3A470%2D474%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Moffatt, M.F., Kabesch, M., Liang, L., Dixon, A. L., Strachan, D., Heath, S., Depner, M., von Berg, A., Bufe, A., Rietschel, E., et al. (2007). Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 448:470-474.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Moffatt,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Moffatt,&as_ylo=2007&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Mizuno%2C S%2E%2C Ogishima%2C S%2E%2C Kitatani%2C K%2E%2C Kikuchi%2C M%2E%2C Tanaka%2C H%2E%2C Yaegashi%2C N%2E%2C and Nakaya%2C J%2E %282016%29%2E Network analysis of a comprehensive knowledge repository reveals a dual role for ceramide in Alzheimer%27s disease%2E PLoS ONE%2E 11%3A e0148431%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Mizuno, S., Ogishima, S., Kitatani, K., Kikuchi, M., Tanaka, H., Yaegashi, N., and Nakaya, J. (2016). Network analysis of a comprehensive knowledge repository reveals a dual role for ceramide in Alzheimer's disease. PLoS ONE. 11: e0148431.

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http://search.crossref.org/?page=1&rows=2&q=Msanne, J., Chen, M., Luttgeharm, K.D., Bradley, A.M., Mays, E. S., Paper, J.M., Boyle, D. L., Cahoon, R.E., Schrick, K., and Cahoon, E.B. (2015). Glucosylceramide is critical for cell-type differentiation and organogenesis, but not for cell viability in Arabidopsis. Plant J. 84: 188-201.

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http://search.crossref.org/?page=1&rows=2&q=Niles, B. J., Mogri, H., Hill, A., Valhakis, A., and Powers, T. (2012). Plasma membrane recruitment and activation of the AGC kinase Ypk1 is mediated by target of rapamycin complex2 (TORC2) and its effector proteins Slm1 and Slm2. Proc Natl Acad Sci.109:1536-1541.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Niles,&hl=en&c2coff=1

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http://search.crossref.org/?page=1&rows=2&q=Okamoto, H., Takuwa, N., Yokomizo, T., Sugimoto, N., Sakurada, S., Shigematsu, H. and Takuwa, Y. (2000). Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3. Mol. Cell. Biol. 20: 9247-9261.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Okamoto,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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http://www.ncbi.nlm.nih.gov/pubmed?term=Park%2C T%2ES%2E%2C Panek%2C R%2EL%2E%2C Rekhter%2C M%2ED%2E%2C Mueller%2C S%2EB%2E%2C Rosebury%2C W%2ES%2E%2C Robertson%2C A%2E%2C Hanselman%2C J%2EC%2E%2C Kindt%2C E%2E%2C Homan%2C R%2E%2C and Karathanasis%2C S%2EK%2E %282006%29%2E Modulation of lipoprotein metabolism by inhibition of sphingomyelin synthesis in ApoE knockout mice%2E Atherosclerosis%2E 189%3A264 %2D272%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Park, T.S., Panek, R.L., Rekhter, M.D., Mueller, S.B., Rosebury, W.S., Robertson, A., Hanselman, J.C., Kindt, E., Homan, R., and Karathanasis, S.K. (2006). Modulation of lipoprotein metabolism by inhibition of sphingomyelin synthesis in ApoE knockout mice. Atherosclerosis. 189:264 -272.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Park,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Modulation of lipoprotein metabolism by inhibition of sphingomyelin synthesis in ApoE knockout mice&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Modulation of lipoprotein metabolism by inhibition of sphingomyelin synthesis in ApoE knockout mice&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Park,&as_ylo=2006&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Peer%2C M%2E%2C Stegmann%2C M%2E%2C Mueller%2C M%2EJ%2E%2C and Waller%2C F%2E %282010%29%2E Pseudomonas syringae infection triggers de novo synthesis of phytosphingosine from sphinganine in Arabidopsis thaliana%2E FEBS letters%2E 84%3A4053%2D4056%2E&dopt=abstract

CrossRef: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Roelants, F. M., Breslow, D.K., Muir, A., Weissman, J.S., and Thorner, J. (2011). Protein kinase Ypk1 phosphorylates regulatoryproteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae. Proc Natl Acad Sci. 108:19222-19227.


Saucedo-García, M., Guevara-García, A., González-Solís, A., Cruz-García, F., Vázquez-Santana, S., Markham, J.E., Lozano-Rosas,M.G., Dietrich, C.R., Ramos-Vega, M., Cahoon, E.B., and Gavilanes-Ruíz, M. (2011). MPK6, sphinganine and the LCB2a gene fromserine palmitoyltransferase are required in the signaling pathway that mediates cell death induced by long chain bases inArabidopsis. New Phytol. 191:943-957.


Schwab, R., Ossowski, S., Riester, M., Warthmann, N., and Weigel, D. (2006). Highly specific gene silencing by artificial microRNAsin Arabidopsis. Plant Cell. 18:1121-1133.


Sentelle, R.D., Senkal, C.E., Jiang, W., Ponnusamy, S., Gencer, S., Selvam, S.P., Ramshesh, V. K., Peterson, Y.K., Lemasters, J.J.,Szulc, Z. M., Bielawski, J., and Ogretmen, B. (2012). Ceramide targets autophagosomes to mitochondria and induces lethalmitophagy. Nature Chem Biol. 8: 831-838.


Shi, C., Yin, J., Liu, Z., Wu, J.X., Zhao, Q., Ren, J., and Yao, N. (2015). A systematic simulation of the effect of salicylic acid onsphingolipid metabolism. Front Plant Sci. 6:186.


Shi, L., Bielawski, J., Mu, J., Dong, H., Teng, C., Zhang, J., Yang, X., Tomishige, N., Hanada, K., Hannun, Y.A., and Zuo, J. (2007).Involvement of sphingoid bases in mediating reactive oxygen intermediate production and programmed cell death in Arabidopsis.Cell Research. 17:1030-1040.


Shimobayashi, M., Oppliger, W., Moes, S., Jeno, P., and Hall, M.N. (2013). TORC1-regulated protein kinase Npr1 phosphorlates Ormto stimulate complex sphingolipid synthesis. Mol Biol Cell. 24:870-881.


Siow, D.L., and Wattenberg, B.W. (2012). Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis. JBiol Chem. 287:40198-40204.


Summers, S.A., and Nelson, D.H. (2005). A role for sphingolipids in producing the common features of type 2 diabetes, metabolicsyndrome X, and Cushing's syndrome. Diabetes. 54: 591-602.


Sun, Y., Miao, Y., Yamane, Y., Zhang, C., Shokat, K. M., Takematsu, H., Kozutsumi, Y., Drubin, D.G. (2012). Orm proteinphosphoregulation mediates transient sphingolipid biosynthesis response to heat stress via Pkh-Ypk and Cdc55-PP2A pathways.Mol Biol Cell. 23:2388-2398.


Tafesse, F.G, and Hoithuis, J.C.M. (2010). A brake on lipid synthesis. Nature. 463:1028-1029.Pubmed: Author and TitleCrossRef: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Teng, C., Dong, H., Shi, L., Deng, Y., Mu, J., Zhang, J., Yang, X., and Zuo, J. (2008). Serine palmitoyltransferase, a key enzyme for denovo synthesis of sphingolipids, is essential for male gametophyte development in Arabidopsis. Plant Physiol.146:1322-1332.


Ternes, P., Feussner, K., Werner, S., Lerche, J., Iven, T., Heilmann, I., Riezman, H., and Feussner, I. (2011). Disruption of the

http://search.crossref.org/?page=1&rows=2&q=Peer, M., Stegmann, M., Mueller, M.J., and Waller, F. (2010). Pseudomonas syringae infection triggers de novo synthesis of phytosphingosine from sphinganine in Arabidopsis thaliana. FEBS letters. 84:4053-4056.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Peer,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Pseudomonas syringae infection triggers de novo synthesis of phytosphingosine from sphinganine in Arabidopsis thaliana&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Pseudomonas syringae infection triggers de novo synthesis of phytosphingosine from sphinganine in Arabidopsis thaliana&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Peer,&as_ylo=2010&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Roelants%2C F%2E M%2E%2C Breslow%2C D%2EK%2E%2C Muir%2C A%2E%2C Weissman%2C J%2ES%2E%2C and Thorner%2C J%2E %282011%29%2E Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae%2E Proc Natl Acad Sci%2E 108%3A19222%2D19227%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Roelants, F. M., Breslow, D.K., Muir, A., Weissman, J.S., and Thorner, J. (2011). Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae. Proc Natl Acad Sci. 108:19222-19227.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Roelants,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Roelants,&as_ylo=2011&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Saucedo%2DGarc�a%2C M%2E%2C Guevara%2DGarc�a%2C A%2E%2C Gonz�lez%2DSol�s%2C A%2E%2C Cruz%2DGarc�a%2C F%2E%2C V�zquez%2DSantana%2C S%2E%2C Markham%2C J%2EE%2E%2C Lozano%2DRosas%2C M%2EG%2E%2C Dietrich%2C C%2ER%2E%2C Ramos%2DVega%2C M%2E%2C Cahoon%2C E%2EB%2E%2C and Gavilanes%2DRu�z%2C M%2E %282011%29%2E MPK6%2C sphinganine and the LCB2a gene from serine palmitoyltransferase are required in the signaling pathway that mediates cell death induced by long chain bases in Arabidopsis%2E New Phytol%2E 191%3A943%2D957%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Saucedo-Garc�a, M., Guevara-Garc�a, A., Gonz�lez-Sol�s, A., Cruz-Garc�a, F., V�zquez-Santana, S., Markham, J.E., Lozano-Rosas, M.G., Dietrich, C.R., Ramos-Vega, M., Cahoon, E.B., and Gavilanes-Ru�z, M. (2011). MPK6, sphinganine and the LCB2a gene from serine palmitoyltransferase are required in the signaling pathway that mediates cell death induced by long chain bases in Arabidopsis. New Phytol. 191:943-957.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Saucedo-Garc�a,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Saucedo-Garc�a,&as_ylo=2011&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Schwab%2C R%2E%2C Ossowski%2C S%2E%2C Riester%2C M%2E%2C Warthmann%2C N%2E%2C and Weigel%2C D%2E %282006%29%2E Highly specific gene silencing by artificial microRNAs in Arabidopsis%2E Plant Cell%2E 18%3A1121%2D1133%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Schwab, R., Ossowski, S., Riester, M., Warthmann, N., and Weigel, D. (2006). Highly specific gene silencing by artificial microRNAs in Arabidopsis. Plant Cell. 18:1121-1133.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Schwab,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Highly specific gene silencing by artificial microRNAs in Arabidopsis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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http://www.ncbi.nlm.nih.gov/pubmed?term=Sentelle%2C R%2ED%2E%2C Senkal%2C C%2EE%2E%2C Jiang%2C W%2E%2C Ponnusamy%2C S%2E%2C Gencer%2C S%2E%2C Selvam%2C S%2EP%2E%2C Ramshesh%2C V%2E K%2E%2C Peterson%2C Y%2EK%2E%2C Lemasters%2C J%2EJ%2E%2C Szulc%2C Z%2E M%2E%2C Bielawski%2C J%2E%2C and Ogretmen%2C B%2E %282012%29%2E Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy%2E Nature Chem Biol%2E 8%3A 831%2D838%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Sentelle, R.D., Senkal, C.E., Jiang, W., Ponnusamy, S., Gencer, S., Selvam, S.P., Ramshesh, V. K., Peterson, Y.K., Lemasters, J.J., Szulc, Z. M., Bielawski, J., and Ogretmen, B. (2012). Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nature Chem Biol. 8: 831-838.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Sentelle,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Sentelle,&as_ylo=2012&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Shi%2C C%2E%2C Yin%2C J%2E%2C Liu%2C Z%2E%2C Wu%2C J%2EX%2E%2C Zhao%2C Q%2E%2C Ren%2C J%2E%2C and Yao%2C N%2E %282015%29%2E A systematic simulation of the effect of salicylic acid on sphingolipid metabolism%2E Front Plant Sci%2E 6%3A186%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Shi, C., Yin, J., Liu, Z., Wu, J.X., Zhao, Q., Ren, J., and Yao, N. (2015). A systematic simulation of the effect of salicylic acid on sphingolipid metabolism. Front Plant Sci. 6:186.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Shi,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=A systematic simulation of the effect of salicylic acid on sphingolipid metabolism&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=A systematic simulation of the effect of salicylic acid on sphingolipid metabolism&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Shi,&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Shi%2C L%2E%2C Bielawski%2C J%2E%2C Mu%2C J%2E%2C Dong%2C H%2E%2C Teng%2C C%2E%2C Zhang%2C J%2E%2C Yang%2C X%2E%2C Tomishige%2C N%2E%2C Hanada%2C K%2E%2C Hannun%2C Y%2EA%2E%2C and Zuo%2C J%2E %282007%29%2E Involvement of sphingoid bases in mediating reactive oxygen intermediate production and programmed cell death in Arabidopsis%2E Cell Research%2E 17%3A1030%2D1040%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Shi, L., Bielawski, J., Mu, J., Dong, H., Teng, C., Zhang, J., Yang, X., Tomishige, N., Hanada, K., Hannun, Y.A., and Zuo, J. (2007). Involvement of sphingoid bases in mediating reactive oxygen intermediate production and programmed cell death in Arabidopsis. Cell Research. 17:1030-1040.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Shi,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Involvement of sphingoid bases in mediating reactive oxygen intermediate production and programmed cell death in Arabidopsis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Involvement of sphingoid bases in mediating reactive oxygen intermediate production and programmed cell death in Arabidopsis&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Shi,&as_ylo=2007&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Shimobayashi%2C M%2E%2C Oppliger%2C W%2E%2C Moes%2C S%2E%2C Jeno%2C P%2E%2C and Hall%2C M%2EN%2E %282013%29%2E TORC1%2Dregulated protein kinase Npr1 phosphorlates Orm to stimulate complex sphingolipid synthesis%2E Mol Biol Cell%2E 24%3A870%2D881%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Shimobayashi, M., Oppliger, W., Moes, S., Jeno, P., and Hall, M.N. (2013). TORC1-regulated protein kinase Npr1 phosphorlates Orm to stimulate complex sphingolipid synthesis. Mol Biol Cell. 24:870-881.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Shimobayashi,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=TORC1-regulated protein kinase Npr1 phosphorlates Orm to stimulate complex sphingolipid synthesis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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http://www.ncbi.nlm.nih.gov/pubmed?term=Siow%2C D%2EL%2E%2C and Wattenberg%2C B%2EW%2E %282012%29%2E Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis%2E J Biol Chem%2E 287%3A40198%2D40204%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Siow, D.L., and Wattenberg, B.W. (2012). Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis. J Biol Chem. 287:40198-40204.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Siow,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Siow,&as_ylo=2012&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Summers%2C S%2EA%2E%2C and Nelson%2C D%2EH%2E %282005%29%2E A role for sphingolipids in producing the common features of type 2 diabetes%2C metabolic syndrome X%2C and Cushing%27s syndrome%2E Diabetes%2E 54%3A 591%2D602%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Summers, S.A., and Nelson, D.H. (2005). A role for sphingolipids in producing the common features of type 2 diabetes, metabolic syndrome X, and Cushing's syndrome. Diabetes. 54: 591-602.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Summers,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=A role for sphingolipids in producing the common features of type 2 diabetes, metabolic syndrome X, and Cushing's syndrome&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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http://www.ncbi.nlm.nih.gov/pubmed?term=Sun%2C Y%2E%2C Miao%2C Y%2E%2C Yamane%2C Y%2E%2C Zhang%2C C%2E%2C Shokat%2C K%2E M%2E%2C Takematsu%2C H%2E%2C Kozutsumi%2C Y%2E%2C Drubin%2C D%2EG%2E %282012%29%2E Orm protein phosphoregulation mediates transient sphingolipid biosynthesis response to heat stress via Pkh%2DYpk and Cdc55%2DPP2A pathways%2E Mol Biol Cell%2E 23%3A2388%2D2398%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Sun, Y., Miao, Y., Yamane, Y., Zhang, C., Shokat, K. M., Takematsu, H., Kozutsumi, Y., Drubin, D.G. (2012). Orm protein phosphoregulation mediates transient sphingolipid biosynthesis response to heat stress via Pkh-Ypk and Cdc55-PP2A pathways. Mol Biol Cell. 23:2388-2398.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Sun,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Orm protein phosphoregulation mediates transient sphingolipid biosynthesis response to heat stress via Pkh-Ypk and Cdc55-PP2A pathways&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Orm protein phosphoregulation mediates transient sphingolipid biosynthesis response to heat stress via Pkh-Ypk and Cdc55-PP2A pathways&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Sun,&as_ylo=2012&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Tafesse%2C F%2EG%2C and Hoithuis%2C J%2EC%2EM%2E %282010%29%2E A brake on lipid synthesis%2E Nature%2E 463%3A1028%2D1029%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Tafesse, F.G, and Hoithuis, J.C.M. (2010). A brake on lipid synthesis. Nature. 463:1028-1029.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Tafesse,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=A brake on lipid synthesis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=A brake on lipid synthesis&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Tafesse,&as_ylo=2010&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Teng%2C C%2E%2C Dong%2C H%2E%2C Shi%2C L%2E%2C Deng%2C Y%2E%2C Mu%2C J%2E%2C Zhang%2C J%2E%2C Yang%2C X%2E%2C and Zuo%2C J%2E %282008%29%2E Serine palmitoyltransferase%2C a key enzyme for de novo synthesis of sphingolipids%2C is essential for male gametophyte development in Arabidopsis%2E Plant Physiol%2E146%3A1322%2D1332%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Teng, C., Dong, H., Shi, L., Deng, Y., Mu, J., Zhang, J., Yang, X., and Zuo, J. (2008). Serine palmitoyltransferase, a key enzyme for de novo synthesis of sphingolipids, is essential for male gametophyte development in Arabidopsis. Plant Physiol.146:1322-1332.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Teng,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Serine palmitoyltransferase, a key enzyme for de novo synthesis of sphingolipids, is essential for male gametophyte development in Arabidopsis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Serine palmitoyltransferase, a key enzyme for de novo synthesis of sphingolipids, is essential for male gametophyte development in Arabidopsis&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Teng,&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

ceramide synthase LOH1 causes spontaneous cell death in Arabidopsis thaliana. New Phytol. 192:841-854.Pubmed: Author and TitleCrossRef: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Wang, W., Yang, X., Tangchaiburana, S., Ndeh, R., Markham, J. E., Tsegaye, Y., Dunn, T. M., Wang, G.L., Bellizzi, M., Parsons, J.F.,Morrissey, D., Bravo, J.E., Lynch, D.V., and Xiao, S. (2008). An inositolphosphorylceramide synthase is involved in regulation ofplant programmed cell death associated with defense in Arabidopsis. Plant Cell. 20: 3163-3179.


Wu, F.H., Shen, S.C., Lee, L.Y., Lee, S.H., Chan, M.T., and Lin, C.S. (2009). Tape-Arabidopsis Sandwich - a simpler Arabidopsisprotoplast isolation method. Plant Methods. 5:16.


Wu, J.X., Li, J., Liu, Z., Yin, J., Chang, Z.Y., Rong, C., Wu, J.L., Bi, F.C., and Yao, N. (2015). The Arabidopsis ceramidase AtACERfunctions in disease resistance and salt tolerance. Plant J. 81:767-780.


Zhang, H., Huang, L., Li, X.H., Ouyang, Z.G., Yu, Y. M., Li, D.Y., and Song, F.M. (2013).Overexpression of a rice long-chain basekinase gene OsLCBK1 in tobacco improves oxidative stress tolerance. Plant Biotech. 30:9-16.


http://www.ncbi.nlm.nih.gov/pubmed?term=Ternes%2C P%2E%2C Feussner%2C K%2E%2C Werner%2C S%2E%2C Lerche%2C J%2E%2C Iven%2C T%2E%2C Heilmann%2C I%2E%2C Riezman%2C H%2E%2C and Feussner%2C I%2E %282011%29%2E Disruption of the ceramide synthase LOH1 causes spontaneous cell death in Arabidopsis thaliana%2E New Phytol%2E 192%3A841%2D854%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Ternes, P., Feussner, K., Werner, S., Lerche, J., Iven, T., Heilmann, I., Riezman, H., and Feussner, I. (2011). Disruption of the ceramide synthase LOH1 causes spontaneous cell death in Arabidopsis thaliana. New Phytol. 192:841-854.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Ternes,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Disruption of the ceramide synthase LOH1 causes spontaneous cell death in Arabidopsis thaliana&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Disruption of the ceramide synthase LOH1 causes spontaneous cell death in Arabidopsis thaliana&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Ternes,&as_ylo=2011&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Wang%2C W%2E%2C Yang%2C X%2E%2C Tangchaiburana%2C S%2E%2C Ndeh%2C R%2E%2C Markham%2C J%2E E%2E%2C Tsegaye%2C Y%2E%2C Dunn%2C T%2E M%2E%2C Wang%2C G%2EL%2E%2C Bellizzi%2C M%2E%2C Parsons%2C J%2EF%2E%2C Morrissey%2C D%2E%2C Bravo%2C J%2EE%2E%2C Lynch%2C D%2EV%2E%2C and Xiao%2C S%2E %282008%29%2E An inositolphosphorylceramide synthase is involved in regulation of plant programmed cell death associated with defense in Arabidopsis%2E Plant Cell%2E 20%3A 3163%2D3179%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Wang, W., Yang, X., Tangchaiburana, S., Ndeh, R., Markham, J. E., Tsegaye, Y., Dunn, T. M., Wang, G.L., Bellizzi, M., Parsons, J.F., Morrissey, D., Bravo, J.E., Lynch, D.V., and Xiao, S. (2008). An inositolphosphorylceramide synthase is involved in regulation of plant programmed cell death associated with defense in Arabidopsis. Plant Cell. 20: 3163-3179.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Wang,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=An inositolphosphorylceramide synthase is involved in regulation of plant programmed cell death associated with defense in Arabidopsis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=An inositolphosphorylceramide synthase is involved in regulation of plant programmed cell death associated with defense in Arabidopsis&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wang,&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Wu%2C F%2EH%2E%2C Shen%2C S%2EC%2E%2C Lee%2C L%2EY%2E%2C Lee%2C S%2EH%2E%2C Chan%2C M%2ET%2E%2C and Lin%2C C%2ES%2E %282009%29%2E Tape%2DArabidopsis Sandwich %2D a simpler Arabidopsis protoplast isolation method%2E Plant Methods%2E 5%3A16%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Wu, F.H., Shen, S.C., Lee, L.Y., Lee, S.H., Chan, M.T., and Lin, C.S. (2009). Tape-Arabidopsis Sandwich - a simpler Arabidopsis protoplast isolation method. Plant Methods. 5:16.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Wu,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=Tape-Arabidopsis Sandwich - a simpler Arabidopsis protoplast isolation method&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=Tape-Arabidopsis Sandwich - a simpler Arabidopsis protoplast isolation method&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wu,&as_ylo=2009&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Wu%2C J%2EX%2E%2C Li%2C J%2E%2C Liu%2C Z%2E%2C Yin%2C J%2E%2C Chang%2C Z%2EY%2E%2C Rong%2C C%2E%2C Wu%2C J%2EL%2E%2C Bi%2C F%2EC%2E%2C and Yao%2C N%2E %282015%29%2E The Arabidopsis ceramidase AtACER functions in disease resistance and salt tolerance%2E Plant J%2E 81%3A767%2D780%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Wu, J.X., Li, J., Liu, Z., Yin, J., Chang, Z.Y., Rong, C., Wu, J.L., Bi, F.C., and Yao, N. (2015). The Arabidopsis ceramidase AtACER functions in disease resistance and salt tolerance. Plant J. 81:767-780.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Wu,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=The Arabidopsis ceramidase AtACER functions in disease resistance and salt tolerance&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=The Arabidopsis ceramidase AtACER functions in disease resistance and salt tolerance&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wu,&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

http://www.ncbi.nlm.nih.gov/pubmed?term=Zhang%2C H%2E%2C Huang%2C L%2E%2C Li%2C X%2EH%2E%2C Ouyang%2C Z%2EG%2E%2C Yu%2C Y%2E M%2E%2C Li%2C D%2EY%2E%2C and Song%2C F%2EM%2E %282013%29%2EOverexpression of a rice long%2Dchain base kinase gene OsLCBK1 in tobacco improves oxidative stress tolerance%2E Plant Biotech%2E 30%3A9%2D16%2E&dopt=abstract

http://search.crossref.org/?page=1&rows=2&q=Zhang, H., Huang, L., Li, X.H., Ouyang, Z.G., Yu, Y. M., Li, D.Y., and Song, F.M. (2013).Overexpression of a rice long-chain base kinase gene OsLCBK1 in tobacco improves oxidative stress tolerance. Plant Biotech. 30:9-16.

http://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Zhang,&hl=en&c2coff=1

http://scholar.google.com/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

http://scholar.google.com/scholar?as_q=&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Zhang,&as_ylo=2013&as_allsubj=all&hl=en&c2coff=1

DOI 10.1105/tpc.16.00574; originally published online December 6, 2016;Plant Cell

Sahu and Nan YaoJian Li, Jian Yin, Chan Rong, Kai-En Li, Jian-Xin Wu, Li-Qun Huang, Hong-Yun Zeng, Sunil Kumar

Contribute to Sphingolipid Homeostasis and Stress Responses in ArabidopsisOrosomucoid Proteins Interact with the Small Subunit of Serine Palmitoyltransferase and

This information is current as of May 21, 2018

Supplemental Data /content/suppl/2016/12/06/tpc.16.00574.DC1.html

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