Mammalian Sperm Motility
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Transcript of Mammalian Sperm Motility
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from meiotic division to sperm maturation. In eukar-
yotic cells, one of the most common mechanisms for
regulating protein activity is the addition and=or
removal of phosphate groups from serine, threonine
or tyrosine residues of protein moieties. Addition or
removal of phosphate can induce allosteric
modifications resulting in conformational changes
in proteins leading either to their activation or
inactivation. These processes are regulated by bothprotein kinases and protein phosphatases. In con-
trast to protein kinases that add a phosphate group
to the hydroxyl group of serine, threonine or tyro-
sine residues, phosphatases remove it. In mam-
malian spermatozoa, the ability to actively swim is
acquired during the transit through the epididymis
under the control of different factors, such as cAMP,
intracellular pH, intracellular calcium and phosphor-
ylation of sperm proteins. As the acquisition of func-
tional competence including gaining motility during
epididymal transit occurs in the complete absence ofcontemporaneous gene transcription and translation
on the part of the spermatozoa, it is widely
accepted that post-translational modifications are
the only means by which spermatozoa can become
competent.
PP1 Isoforms and their Interacting
Proteins (PIPs)
The protein serine=threonine phosphatases (PPs)
specifically hydrolyze serine=threonine phosphoe-sters, and are metalloproteins with extremely
diverse and unrelated functions [Cohen 2002]. As a
holoenzyme, the PPs have catalytic subunits and
regulatory subunits. The catalytic subunits are div-
ided into four major groups, including protein
phosphatase 1 (PP1), protein phosphatase 2A
(PP2A), protein phosphatase 2B (PP2B) and protein
phosphatase 2C (PP2C). In mammals, there are four
homologous isoforms of type 1 serine=threonine
protein phosphatase (PP1a, PP1b=d, PP1c1 and
PP1c2) [Bollen and Stalmans 1992]. These isoformsshare >89% identity and are encoded by three dis-
tinct genes, with PP1c1 and PP1c2 produced from
the alternative splicing of the same primary tran-
script. The isoforms of PP1 vary in sequence at
their extreme amino and carboxyl termini.
Functions of PP1 include controlling metabolism,
cell division, apoptosis and protein synthesis
by dephosphorylation of key regulatory proteins
[Cohen 2002; Bollen 2001; Ceulemans et al. 2002;
Ceulemans and Bollen, 2004). All PP1s contain a
Thr-Pro-Pro-Arg (TPPR) amino acid sequence
segment at their carboxyl terminal, which is a
consensus sequence for phosphorylation by
cyclin-dependent kinases (Cdks). Phosphorylation
of PP1 by Cdk1 and Cdk2 in somatic cells reduces
the catalytic activity of this enzyme [Cohen 2002;Dohadwala et al. 1994; Kwon et al. 1997; Liu et al.
1999].
PP1s do not exist freely in the cell but are
associated with a large variety of polypeptides that
determine when and where PP1 acts. These PIPs
(also called regulatory subunits) function as
activity-modulators, targeting subunits and=or sub-
strates. Hormones, growth factors and metabolites
control the function of the PP1 holoenzymes mainly
by modulating the interaction of the subunits. The
available information suggests that these PIPs inter-act with PP1 via multiple, short-sequence motifs.
The PIPs are structurally quite different, but almost
all have a consensus binding motif (RK)-x0-1-
(VI)-{P}-(FW), where x denotes any residue and {P}
any residue except Pro, and it is often called simply
the RVxF-motif. The RVxF-motif binds to a hydro-
phobic channel near the C-terminus of PP1. The
binding of the RVxF-motif not only has a PP1
anchoring function but also promotes the interaction
of secondary, lower-affinity binding sites, often
resulting in an altered activity and=or substratespecificity of PP1. The F-x-x-(RK)-x-(RK) motif
represents a new consensus sequence for the recog-
nition and binding of some Bcl-2 proteins to PP1
[Ayllon et al. 2002].
Currently, about 70 mammalian genes coding for
more than 60 PIPs have been identified [Garcia-
Gimeno et al. 2003]. Given there are approximately
10,000 phosphoproteins in mammals, many PIPs
remain to be discovered. PIPs can be classified into
mainly 8 categories of: glycogen metabolism, myofi-
briella, nuclear, endoplasmic-ribosomal, plasmamembrane=cytoskeleton centrosome=microtubule,
apoptosis and specific substrates and inhibitors. In
addition to inhibitor-1 (I1) and inhibitor-2 (I2)
representing two different ways of inhibiting PP1
phosphatase activity, there are also other protein
phosphatase inhibitors without a clear mechanism
[Garcia-Gimeno et al. 2003; Zhang et al. 1998;
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Hrabchak and Varmuza 2004; Mishra et al. 2003;
Vijayaraghavan et al. 1996; Smith et al. 1996]. I1
activity is regulated by cAMP-dependent phosphory-
lation of a single threonine residue by protein kinase
A (PKA) and by calcium=calmodulin-dependent
dephosphorylation of the same residue [Shenolikar
and Nairn 1991; Cohen 1989]. I2 binds to the catalytic
subunit of PP1 to form an inactive cytoplasmic form
of the enzyme (PP1I2) that can be converted toactive PP1 by phosphorylation of the bound I2 by
glycogen synthase kinase-3 [Bollen and Stalmans
1992; Cohen 1989; Hemmings et al. 1982]. In sperma-
tozoa of mice, a novel PP1 inhibitor 3 (I3) containing
both the RVxF-motif, nuclear localization signals
(NLS) and nuclear targeting signals (NTS) has been
discovered [Huang et al. 2005a; Han et al. 2007]. I1,
I2 and I3 are heat-stable proteins all enriched in pro-
line [Zhang et al. 1998]. It has been shown that PP1s
nuclear translocation and nuclear retention depend
on binding to RVxF-motif interactors [Lesage et al.2004]. The PP1 nuclear interactors include PNUTS,
Sds22, NIPP and SIPP1 that have both the RVxF-motif
and NLS.
Expression Localization and Possible
Functions of PP1 Isoforms
PP1 is expressed in various cellular compartments
but is most abundant in the nucleus. PP1a, PP1cand
PP1bare closely related isoforms with distinct locali-
zation patterns. In somatic cells, PP1a, PP1c andPP1b are primarily located in the nucleus. PP1a is
mainly attached to the nuclear matrix, while PP1c
is predominantly found in the nucleoli. PP1b is
present in the non-nucleolar chromatin fraction and
the nucleoli [Andreassen et al. 1998; Twinkle-Mul-
cahy et al. 2001; Twinkle-Mulcahy et al. 2003]. Using
the fluorescent fusion proteins, isoforms of PP1 have
been delicately located in mammalian cells cultured
in vitro. During interphase, PP1cwas found in both
cytoplasmic and nucleoplasmic pools, showing a
prominent accumulation within nucleoli, targetingto kinetochores and chromatin. This implicates
PP1c in multiple regulatory pathways, in agreement
with previous studies linking its activity to the
regulation of transcription, chromatin remodeling,
chromosome condensation and segregation, cytokin-
esis, and reassembly of the nuclear envelope. PP1ais
largely excluded from the nucleoli found mainly in a
diffuse pool and in a few as-yet-unidentified foci
[Twinkle-Mulcahy et al. 2006].
In addition to the nucleus, PP1 is also found
within the axoneme. PP1c is anchored in the central
pair apparatus of the axoneme in Chlamydomonas
flagellar [Yang et al. 2000]. Ciliary and flagellar
motility is controlled by phosphorylation [Brokaw
1987; Satir et al. 1993; Tash and Bracho 1994]. PP1
may be involved in the regulation of flagellar motilitytogether with protein kinases [San Agustin and
Witman 1994; Chaudhry et al. 1995]. Recently, PP1
was found to be involved in regulating the acqui-
sition of motility [Huang et al. 2004; Huang et al.
2004b; Huang et al. 2005b].
Function and Expression of PP1/PIPs
in the Testis, Epididymis and
Spermatozoa
In the Testis
PP1a, PP1band PP1care all expressed in the testis
[Tash and Bracho 1994]. Higher levels of PP1ain con-
densing spermatids and lower levels in other germ
cell stages have been found. While PP1c1 is ubiqui-
tously expressed, PP1c2 is conserved and expressed
in the testis, spermatozoa and brain [Andreassen
et al. 1998; Smith et al. 1996; Huang et al. 2002;
Kitagawa et al. 1990]. PP1c2 is expressed in the nuclei
of germ cells from the pachytene spermatocyte stage
through the early spermatid stages, and in the sper-matozoa head and flagella [Shima et al. 1993; Huang
et al. 2004a; Huang et al. 2004b; Huang et al. 2005b].
The function of PP1c has been confirmed by
PP1c= knock-out mice [Varmuza et al. 1999]. Males
homozygous for a null mutation of PP1c gene are
sterile, and display both germ cell and Sertoli cell
defects. Histopathology from PP1c mutants indi-
cates a more complex role for this protein in
spermatogenesis. More than one defect is observed
in mutant mice. The defects include elevated
serum FSH [Oppedisano-Wells et al. 2002], increasedDNA fragmentation in germ cells [Jurisicova et al.
1999] and increased aneuploidy in haploid gametes
[Oppedisano-Wells et al. 2002]. Loss of spermatids
begins at the round spermatid stage and increases
in severity such that there is a marked reduction in
elongating and condensing spermatids and an almost
complete absence of mature sperm. Meiosis may be
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disrupted giving rise to polyploid spermatids.
Interestingly, histones remain complexed with
spermatid chromatin beyond when they are nor-
mally removed and replaced by protamines. Normal
staging is disrupted in PP1 mutants. Some cell types
are reduced in number, but none are absolutely
missing [Varmuza et al. 1999]. A chimeric testis with
wild type of Sertoli cells and PP1c= spermatids
revealed intermediate phenotypes when comparedwith PP1c= . They did not sire pups derived from
mutant germ cells, suggesting that expression of
PP1c2 genes may be restricted to the spermatozoon
[Oppedisano-Wells and Varmuza 2003].
Spermatogenic zip protein 1 (Spz1) has been
identified as binding to the PP1c2 splice variant in
the mouse testis [Hrabchak and Varmuza 2004].
Spz1 was a member of the basic helix-loop-helix
family of transcription factors. Overexpression of
spz1 and loss of PP1 c in the testis show similar phe-
notypes such as spermatogenic arrest and germ cellapoptosis [Hsu et al. 2004].
In the Epididymis and Spermatozoa
Human and primate sperm extracts contain PP
activity that might be from PP1c2 or PP2A [Smith
et al. 1996], whereas sea urchin [Swarup and
Garbers 1992; Tash et al. 1988], caprine [Barua et al.
1985], canine and porcine [Tash et al. 1988] sperm
extracts primarily contain PP2B (Calcineurin)
activity. In bovine sperm extracts contain bothPP2B and PP1 activity [Tash et al. 1988; Hrabchak
and Varmuza 2004; Mishra et al. 2003; Huang et al.
2002; Huang et al. 2004a,b; Huang et al. 2005b;
Varmuza et al. 1999; Oppedisano-Wells and Varmuza
2003; Tang and Hoskins 1975]. In human and pri-
mate spermatozoa, the heat-stable specific inhibitor
of PP1 is neither I1 nor I2 [Smith et al. 1996]. The
I2-like inhibitor is antagonized by the addition of
Glucogen synthase kinase 3 (GSK-3) but the signifi-
cance is not clear. A new PP1 inhibitor I3 has been
identified in mouse spermatozoa [Han et al. 2007].Sds22, 14-3-3 protein and hsp90 are potential regula-
tors of PP1c2. PP1c2 may also regulate epididymal
sperm motility [Hrabchak and Varmuza 2004; Mishra
et al. 2003; Huang et al. 2004a,b; Huang et al. 2005b;
Huang et al. 2002; Shima et al. 1993; Jurisicova et al.
1999]. Phosphorylation of PP1c2 increases exhibiting
decreased activity during sperm maturation as
motility of spermatozoa increase. Three pools of
PP1c2 in caudal and caput epididymal spermatozoa
are found. The caput pool includes the active form
of PP1c2, phosphorylated and an active form of
14-3-3 binding PP1 c2 and the inactive form of
hsp90 binding PP1 c2. The cauda pool includes the
inactive form of sds22 binding PP1c2 [Mishra et al.
2003], phosphorylated and an active form of 14-3-3
binding PP1c2 and an inactive form of hsp90 bindingPP1c2 [Huang et al. 2004a,b]. PP1c2 is inactivated by
binding to sds22 and hsp90 while PP1c2 is activated
and phosphorylated by binding to 14-3-3 protein
[Huang et al. 2004a; Huang et al. 2002]. Sds22 is a
mammalian homologue of yeast PP1 binding protein
[Huang et al. 2002] belonging to a family of proteins
that contain repeats of leucine-rich 22 amino acid
segment. The 14-3-3 proteins belong to a family of
abundant and widely expressed 2833 kDa acidic
polypeptides that spontaneously self-assemble as
dimmers. The 14-3-3 proteins bind to phosphoserine=threonine containing motifs in a sequence-
specific manner [Yaffe and Elia 2001; Aitken et al.
1992; Tzivion and Avruch 2002]. The Hsp90 is a
highly conserved ATP-dependent chaperone
[Richter and Buchner 2001] and this protein is subject
to tyrosine-phosphorylation during sperm capa-
citation in mice, rats and humans (Ecroyd et al.
2003). Cytosolic PP1 and GSK-3 activities appear to
be inversely related to the motility of monkey epidi-
dymal sperm [Smith et al. 1996]. Higher concen-
tration of GSK-3 and PP1 are present in immotilebovine caput epididymal sperm compated with
motile cauda epididymal sperm, and may control
motility [Vijayaraghavan et al. 1996; Miki et al.
2004; Somanath et al. 2004].
Some Other Estimated PIPs from Database
Expressed in the Testis and/or Spermatozoa
As mentioned above, two distinct docking consen-
sus motifs (RK)-x0-1-(VI)-{P}-(FW) and F-x-x-(RK)-x-
(RK) have been identified in PIPs. The PIPs databaseat http://pp1signature.pasteur.fr/ includes all discov-
ered proteins containing the two motifs. These
include transcription factors, transport proteins as
well as kinases.
A putative transcription factor or DNA-associated
protein called SARP (several ankyrin repeat protein)
has been identified as a PIP. SARP has 3 splice
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variants, SARP1, SARP2 and SARP3. SARP1 and=or
SARP2 are expressed at high levels in testis and
spermatozoa, where they are shown to interact with
both PP1c1 and PP1c2. SARP is highly abundant in
the nucleus of mammalian cells, consistent with the
putative nuclear localization signal at the N-terminus.
The presence of a lucine zipper near the C-terminus
of SARP1 and SARP2, and the binding of mammalian
DNA to SARP2, suggests that SARP1 and SARP2 maybe transcription factors or DNA-associated proteins
that modulate gene expression [Browne et al. 2007].
Angiotensin-converting enzyme (ACE) is a zinc-
containing dipeptidyl carboxypeptidase widely
distributed in mammalian tissues and is thought to
play a critical role in blood pressure regulation.
Testis contain a unique androgen-dependent ACE
isozyme, ACE-T, that is initially found in post-meiotic
step 3 spermatids and then increases markedly dur-
ing differentiation. ACE-T is strictly confined to the
adluminal membrane face of elongating spermatidsand localizing to the neck and midpiece region of
released and ejaculated spermatozoa [Pauls et al.
2003]. Male mice homozygous for a disrupted ACE
gene are almost infertile, despite showing normal
mating behavior, testis histology and sperm para-
meters Reduced oviduct transport and zona pellu-
cida binding of spermatozoa is observed [Krege
et al. 1995; Hagaman et al. 1998]. It is estimated that
the unique N-terminal of ACE-T bearing specific
binding properties for an oviduct=ovum substrate
may yield male sterility [Kessler et al. 2000].Another putative PIP is testis-specific protein
kinase (Tesk) 2 which is a member of the Tesk family
with 48% amino acid identity with Tesk1. Tesk2,
is predominantly expressed in the nucleus of
Sertoli cells. It phosphorylates cofilin=ADF (actin-
depolymerizing factor) at Ser3 that induces actin
reorganization. Since actin-depolymerizing and
actin-severing activities of cofilin=ADF are abrogated
by phosphorylation at Ser3, TESK2 seems to play an
important role in actin filament dynamics by inhibit-
ing cofilin=ADF activity [Toshima et al. 2001].Fer-1, first discovered inCaenorhabditis elegansis
another putative PIP that is mainly expressed in
spermatocytes. It is prevalent when membranous
organelles (MOs) fuse with the spermatid plasma
membrane. Resembling some viral fusion proteins,
fer-1may play a direct role in MO-plasma membrane
fusion [Achanzar and Ward 1997].
Mechanisms of Spermatozoa Flagellar
Motility Control
The force for flagellar movement is exerted
through the sliding of outer-doublet microtubules.
ATP is required to support coordinated movement
of the central axoneme and surrounding flagellar
structures [Mann and Lutwak-Mann 1981]. This is dri-
ven by dynein molecular motors [Inaba 2003] i.e., thedynein ATPase. Several studies have revealed that
ciliary and flagellar motility is controlled by phos-
phorylation [Brokaw 1987; Satir et al. 1993; Tash
and Brocho 1994; Chaudhry et al. 1995]. In vitro
analysis has indicated that cAMP-dependent protein
Skinase A, phosphatases PP1 and PP2A anchored in
the axoneme are likely involved [Yang et al. 2000; an
Agustin and Witman 1994;Chaudhry et al. 1995; Huang
et al. 1982; Porter et al. 1992; Piperno et al. 1992;
Piperno et al. 1994; Yoshimura and Shingyoji 1999].
Spermatozoa are stored in extratesticular ducts inan immotile state in many animals and their motility
is activated on their release from the ducts. Activation
of motility is inhibited by factors in the extratesticular
plasma. Mammalian spermatozoa from the distal part
of the epididymis show better motility activation than
that from the proximal part of the epididymis as they
acquire the capacity for motility and fertilization dur-
ing epididymal transit. During this passage through
the epididymis, changes are observed in the intra-
cellular second messengerscAMP, pH, calcium
and intra-sperm ATP content [Bedford and Hoskins1990; Cooper 1986]. The relation of sperm motility
activation and other morphological=physiological
change(s) of sperm during spermiogenesis are still
unclear. But, it is known that the potential for
motility already exists in both immature testicular
and epididymal sperm as evidenced by the ability
of demembranated immature sperm to undergo
motility activation [Mohri and Yanagimachi 1980;
Yeung 1984]. Sperm motility in immature spermato-
zoa can be initiated by stimulating protein kinase
activity or inhibiting protein phosphatase activity[Vijayaraghavan et al. 1996; Smith et al. 1996; Smith
et al. 1999]. So, rather than acquiring the capacity
for motility, spermatozoa in the epididymis might
make themselves more sensitive to stimulating fac-
tors by gradually expelling inhibitors or by other
unknown mechanisms. One possible signal is phos-
phorylation=dephosphorylation. Low protein kinase
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and high protein phosphatase activities most likely
limit motility in immature spermatozoa. In a number
of species, development of sperm motility in the epi-
didymis is associated with increased intrasperm
cAMP [Amann et al. 1982; Brandt and Hoskins
1980], associated with decreased glycogen synthase
kinase-3 and protein phosphatase 1 activity [Vijayar-
aghavan et al. 1996]. It is noted that the control fac-
tors of phosphatase to sperm motility might beconfined to the axoneme [Habermacher and
Sale 1996]. This is supported by the observation of
the gain of motility after the addition of protein
phosphatase 1 inhibitors to demembraned fowl
spermatozoa [Ashizawa et al. 1994].
AKAPs [A Kinase Anchor Protein, cAMP-depen-
dent protein kinase anchoring proteins, Miki and
Eddy 1998] are the candidate target of PP1 in sperm
flagella. AKAPs assemble multi-enzyme signaling
complexes in proximity to substrate effector pro-
teins, thus directing and amplifying membrane-generated signals. They form a transduceosome,
an autonomous multivalent scaffold that assembles
and integrates signals derived from multiple path-
ways. The AKAP family shares little overall primary
sequence similarity excluding their functional
domains including the targeting domain (as a scaf-
fold and membrane anchor) and the amphipathic
helical tethering domain (binding to regulatory sub-
units) that are highly conserved. In addition to bind-
ing to cAMP-dependent protein kinases such as
protein kinase A, some AKAPs associate with proteinkinase C and Ser=Thr phosphates.
It has been shown that the amino terminus of
AKAP121, a potential PIP, interacts with mitochon-
drial membranes and with tubulin. Tubulin, a hetero-
dimer composed of two similar acidic isoforms
(a and b) participates in the organization of
eukaryotic microtubule networks. AKAP=PKA or
AKAP=PP1 complexes anchored to spindles might
regulate the dynamic assembly of microtubules by
creating target sites of cAMP action [Cardone et al.
2002]. In contrast to AKAP121, the candidacy ofAKAP4 as PIP is additionally experimentally sup-
ported. AKAP4 is the major fibrous sheath protein
located in the principal piece of spermatozoa. It
serves as a scaffold for proteins in signaling path-
ways involved in sperm maturation, motility, capaci-
tation, hyperactivation and glycolysis. In the
principal piece, the fibrous sheath replaces the
mitochondria sheath. Outer dense fibers 3 and 8
are also substituted by the two longitudinal
columns of the fibrous sheath. AKAP4 recruits PKA
to the fibrous sheath and facilitates local phosphory-
lation to regulate flagellum function. Spermatozoa
from AKAP4= mice lack motility and are infertile
[Miki et al. 2002]. PP1 activity is decreased in the
AKAP4= mice and might indicate the functional
linkage between PP1 and AKAP4 [Huang et al.2005b].
A Hypothesis for the Signaling
Pathways of Mammalian
Spermatozoa Motility Activation
Both the cAMP and Ca2 signal transduction
pathways are involved in activation of motility in
immotile spermatozoa from the cauda epididymis in
rat and mouse [Wade et al. 2003; Schulh et al. 2006].A Ca2 dependent increase in cAMP initiates a signal
transduction cascade for motility activation, which is
independent of protein kinase A-mediated phosphor-
ylation of flagellar proteins in immotile rat spermato-
zoa [Wade et al. 2003]. The concentration of cAMP
increases with activation of motility in spermatozoa
from the cauda epididymis of hamsters [Morton et al.
1974] and rats [Armstrong et al. 1994]. So, cAMP seems
to be the first signal for sperm motility activation.
cAMP-dependent protein kinase (PKA), the major
downstream effector of cAMP signals in sperm, isthen activated and through the AKAPs triggers pro-
tein phosphorylation that might be important for
sperm motility [Si and Okuno 1995; Nolan et al.
2004]. Calmodulin Kinase II (CAMKII) is considered
to be a ubiquitous protein mediating Cai2 signaling
the activation of dynein ATPase in mammalian sperm
[Hsu et al. 2004], and CAMKII-PP1 complex is proven
to act together as a simple device in the Ca2 signal
transduction in the synapses [Bradshaw et al. 2002].
CAMKII can be activated in a persistent manner by
autophospholation at Thr286
. When dephosphory-lated at Thr286 by PP1, CaMKII is deactivated [Nomura
et al. 2004].
Considering activation of the the sperm motility
mechaninism and PP1s=PIPs function during
spermatogenesis we propose the following two-
step signaling pathway of PP1s in controlling sper-
matozoa motility as summarized in Figure 1. In the
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first step, motionless spermatozoa in the caput of the
epididymis need to be conditioned through the
AKAP signal transduction pathway which prepares
the microtubules of the spermatozoa to a ready
state for motility activation. In the second step,
motility of the conditioned spermatozoa is then trig-
gered by Ca2 -CAMKII signal transduction pathway
with a functional dynein ATPase. PP1s are involved
in the two signal transduction pathways by interact-
ing with AKAPs and regulating activity of CAMKII,respectively.
ACKNOWLEDGMENT
This work was supported by a direct grant of the
Chinese University of Hong Kong c001-2041219.
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FIGURE 1 cAMP produced by adenylyl cyclase from ATP stimulates the activity of PKA. AKAPs then link the active PKA to both themicrotubules of the spermatozoa flagella and the membrane of the mitochondria. PKA, now in the proximity of the flagella, then stimulates
the microtubule local factors like dynein ATPase by creating target sites of cAMP and/or other unknown functions and makes the
microtubules conditioned with the ability to respond to Ca2 calmodulin stimulation. AKAPs linked to the mitochondria membrane
might stimulate production of more ATP. PP1 is involved in this pathway by interacting with AKAPs. We hypothesize that the binding
of PP1 to the AKAPs might competitively inhibit their binding to PKA. Before binding to AKAPs, the microtubules are not sensitive to
stimulating signals in the absence of key factors. In contrast, the Ca2 CamKII complex could initiate the motility of the conditioned
microtubules by immediately activating dynein ATPase. Motility is maintained by the continuous consumption of ATP. PP1 could
dephosphorylate and inactivate the CAMKII at Thr286. In both pathways, a decrease in the concentration of PP1 would favor the activation
of sperm motility.
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