Regulation of Organelle and Cell Compartment Signaling: Cell Signaling Collection
Four types of cell-cell signaling - its.caltech.edumbklab/courses/bi113/Lecture 7.pdf · Four types...
Transcript of Four types of cell-cell signaling - its.caltech.edumbklab/courses/bi113/Lecture 7.pdf · Four types...
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Four types of cell-cell signaling
Lodish et al, 2000
(Hormones)
(eg., neural transmission)
(eg., growth factors)
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Signal transduction
Seven transmembrane receptorsG proteins
Lodish et al, 2000
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Lodish et al, 2000
Signal transduction
Cytokine receptors-expression cloningProtein kinases, intracellular signaling-MAPK pathway
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Signal transduction
Seven transmembrane receptorsG proteins
Lodish et al, 2000
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Cooper, 2000
Synthesis of cAMP by adenylate cyclase
(3’-5’- linkage)
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The effects of many hormones aremediated by second messengers
Lodish et al, 2000
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Adenylyl cyclase is a membrane-bound enzyme
Lodish et al, 2000
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G protein-coupled (7 TM) receptors
Lodish et al, 2000
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b-adrenergic effects-fight or flight response-increased heart rate and contractility-vasodilation-bronchodilation
b1 and b2-adrenergic antagonists (b-blockers) are medicallyimportant-hypertension-ischemic heart disease-arrhythmias
-asthma-preterm labor
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Stimulation of b-adrenergic receptorsleads to a rise in cAMP
Lodish et al, 2000
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b-adrenergic receptors mediatethe induction of cAMP synthesis
Lodish et al, 2000
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Model of complex formed between isoproterenoland the b2-adrenergic receptor
Lodish et al, 2000
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Other important G-protein coupled receptors
Muscarinic receptor (acetylcholine) important in brain, sympathetic nervous system, heart
Metabotropic glutamate receptor (glutamate) important in brain
A variety of peptide receptors (ie. Peptide Y, Substance P) mediators of neural signals in gut, brain, and spinal cord
Odorant receptors sensory receptors in the nasal epithelium
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Membrane disks in the outer segments of rod cellscontain rhodopsin, a light-sensitive protein
Lodish et al, 2000
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Rods and cones contain vision receptors
Lodish et al, 2000
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The light-triggered closing of Na+ channelshyperpolarizes rod cells
Lodish et al, 2000
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Absorption of a photon triggers isomerization of retinaland activation of opsin
Figure 21-46
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Structure of rhodopsin and possibleconformational changes
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Light activates rhodopsin/Gs/phosphodiesteraseand hydrolyzes cGMP
Channel closes uponlight activation
Guanylate cyclase regenerates cGMP
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Rod cells adapt to varying levels of ambient light
Lodish et al, 2000
Adaptation-Rhodopsin kinase phosphorylates activatedrhodopsin (up to 7 sites)-Phosphorylated rhodopsin is less efficient inactivating transducin-At high phosphorylation levels, arrestin bindsrhodopsin and prevents binding of transducin
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Color vision utilizes three opsin pigments
Lodish et al, 2000
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Trimeric G protein links b-adrenergic receptorsand adenylyl cyclase
Lodish et al, 2000Multiple amplification steps
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Adenylyl cyclase is stimulated and inhibitedby different receptor-ligand complexes
Lodish et al, 2000
(Prostaglandin)
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Cholera: a diarrheal disease
A acute diarrheal disease- massive watery diarrhea- vomiting- adults can lose up to 1 L/hr
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Vibrio cholera- gram negative rod (bacterium)Native to Ganges river in India; 7 pandemics in since 1911Transmission- fecal contamination of water: Vibrio ingested,colonizes small bowel, produces cholera toxinCholera toxin catalytically transfers ADP-ribose from NAD(nicotine adenine dinucleotide) to Gs proteinGs is permanently upregulated, leading to excess adenylatecyclase activity
V. cholera infections cause unregulatedadenylate cyclase in intestinal cells
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ADP-ribosylation of Gs proteinby cholera toxin
Nicotine adenine dinucleotide(NAD)
ADP-ribosylation
ADP-ribose is added to anarginine residue in GsBlocks GTPase activity
arginine
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-NaCl accumulates in intestinal lumen;massive water loss/diarrhea-Intestinal muscosa intact-untreated, up to 50% death(dehydration/hypovolemic shock)-with glucose/electrolyte replacementtherapy, less than 1% death
Most cholera patients recover withoral rehydration therapy
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Some bacterial toxins irreversibly modify G proteins
Lodish et al, 2000
Also, pertussis toxin ADP-ribosylatesGi and locks Gi in GDP (inactive)state