Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization

Xie, Fang; Garcia, Manuel A.; Carlson, Anne E.; Schuh, Sonya M.; Babcock, Donner F.; Jaiswal, Bijay S.; Gossen, Jan A.; Esposito, Gloria; Duin, Marcel van; Conti, Marco

doi:10.1016/j.ydbio.2006.05.038

Cited by 213 publications

(222 citation statements)

References 48 publications

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“…It is not known whether these functional changes were regulated coordinately or independently. Previously, media conditions or pharmacological treatments dissected the development of hyperactivated sperm motility in vitro from such component events of capacitation as the increased frequency of spontaneous (that is, ZP agonistindependent) acrosome reaction (43,44) or the enhanced tyrosine protein phosphorylation that accompanies capacitation (45,46). Similarly, hyperactivation depends on the function of the Catsper family of cation channels and of Pcma4, the Ca 2ϩ -conducting ATPase (47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

A polycystin-1 controls postcopulatory reproductive selection in mice

Sutton

Jungnickel

Florman

2008

Proc. Natl. Acad. Sci. U.S.A.

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Pkdrej, a member of the polycystin-1 gene family, is expressed only in the male germ line. Male mice that are homozygous for a targeted mutation in the Pkdrej allele (Pkdrej tm/tm ) are fertile in unrestricted mating trials, but exhibit lower reproductive success when competing with wild-type males in sequential mating trials and in artificial insemination of mixed-sperm populations. Following mating, sperm from Pkdrej tm/tm mice require >2 h longer than those of wild-type males to be detected within the egg/cumulus complex in the oviduct. Sperm from mice of both genotypes are able to capacitate in vitro. However, one of the component processes of capacitation, the ability to undergo a zona pellucidaevoked acrosome reaction, develops more slowly in sperm from Pkdrej tm/tm animals than in sperm from wild-type males. In contrast, a second component process of capacitation, the transition to hyperactivated flagellar motility, develops with a similar time course in both genotypes. These two behavioral consequences of capacitation, exocytotic competence and altered motility, are therefore differentially regulated. These data suggest that Pkdrej controls the timing of fertilization in vivo through effects on sperm transport and exocytotic competence and is a factor in postcopulatory sexual selection.capacitation ͉ evolution ͉ fertilization ͉ polycystin ͉ sexual selection

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Section: Discussionmentioning

confidence: 99%

A polycystin-1 controls postcopulatory reproductive selection in mice

Sutton

Jungnickel

Florman

2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Although multiple signal transduction pathways are involved in capacitation, a central role for cAMP as a regulatory mediator is underscored by the male-infertility phenotypes of mice that carry targeted disruptions of the sperm-specific C␣2 catalytic subunit of protein kinase A (PKA) or of the atypical HCO 3 Ϫ -stimulated sperm adenylyl cyclase, SACY (formerly known as sAC). Studies of the mutant sperm that lack C␣2 (2) or SACY (3)(4)(5) have provided definitive evidence that neither protein is required for the initiation of motility or for maintenance of a slow basal flagellar beat. In contrast, both C␣2 and SACY are required for the acceleration of the flagellar beat that characterizes the rapid activation of motility by the HCO 3 Ϫ anion, and for HCO 3 Ϫ to rapidly facilitate evoked entry of Ca 2ϩ .…”

mentioning

confidence: 99%

Tissue-specific PKA inhibition using a chemical genetic approach and its application to studies on sperm capacitation

Morgan¹,

Weisenhaus²,

Shum³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Studies on cAMP signaling and protein kinase A (PKA) function in vivo are limited by the lack of highly specific inhibitors that can be used in primary cell culture and whole animals. Previously we reported that a mutation in the ATP binding pocket of a catalytic subunit (C␣) of PKA confers sensitivity to the pyrazolo[3,4-d]pyrimidine inhibitor, 1NM-PP1. We have now engineered the mouse Pkraca gene such that after Cre-mediated recombination in vivo, the C␣M120A mutant protein is expressed and the wild-type C␣ is turned off. We demonstrate the utility of this approach by examining the requirement for PKA activity during capacitation of sperm from mice that express C␣M120A mutant protein. For C␣M120A sperm, 10 M of 1NM-PP1 prevented PKA-dependent phosphorylation and the activation of motility that are both rapidly (<90 s) evoked by the HCO3 ؊ anion. A continuous (90 min) inhibition with 10 M of 1NM-PP1 prevented the protein tyrosine phosphorylation of late-stage capacitation. Delayed application of 1NM-PP1 demonstrated that PKA activity was required for at least the initial 30 min of capacitation to produce subsequent protein tyrosine phosphorylation. Acute application of 1NM-PP1 rapidly slowed the accelerated beat of activated motility but did not affect the established waveform asymmetry of hyperactivated sperm. Our results demonstrate that PKA in C␣M120A mutant sperm is rapidly and reversibly inhibited by 1NM-PP1 and that this blockade has selective and time-dependent effects on multiple aspects of capacitation. The conditional C␣M120A-expressing mouse lines will be valuable tools for studying PKA function in vivo.cAMP ͉ mouse genetics ͉ protein phosphorylation ͉ male fertility ͉ hyperactivation M ammalian sperm undergo a series of maturational changes in the female reproductive tract and this process, termed capacitation, is essential for subsequent fertilization of the egg (1). Although multiple signal transduction pathways are involved in capacitation, a central role for cAMP as a regulatory mediator is underscored by the male-infertility phenotypes of mice that carry targeted disruptions of the sperm-specific C␣2 catalytic subunit of protein kinase A (PKA) or of the atypical HCO 3 Ϫ -stimulated sperm adenylyl cyclase, SACY (formerly known as sAC). Studies of the mutant sperm that lack C␣2 (2) or SACY (3-5) have provided definitive evidence that neither protein is required for the initiation of motility or for maintenance of a slow basal flagellar beat. In contrast, both C␣2 and SACY are required for the acceleration of the flagellar beat that characterizes the rapid activation of motility by the HCO 3 Ϫ anion, and for HCO 3 Ϫ to rapidly facilitate evoked entry of Ca 2ϩ . The capacitation sequence that prepares sperm for fertilization includes two additional components that also are HCO 3 Ϫ dependent but delayed in onset. These delayed increases in protein tyrosine phosphorylation and hyperactivation of motility do not occur in the C␣2 or SACY null sperm. However, it has remained unclear whether cAMP and PKA...

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“…The stimulation of the sperm soluble adenylate cyclase by HCO 3 − and the consequent cAMP/PKA stimulation is required for the activated motility (Carlson et al 2007 ;Esposito et al 2004 ;Hess et al 2005 ;Nolan et al 2004 ;Xie et al 2006 ). After some time (varying according to species) in the female tract, spermatozoa become hyperactivated, displaying vigorous asymmetrical fl agellar beating with large amplitude and high curvature.…”

Section: Motilitymentioning

confidence: 99%

Cl− Channels and Transporters in Sperm Physiology

Treviño

Orta

Figueiras-Fierro

et al. 2014

Sexual Reproduction in Animals and Plants

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Spermatozoa must decode environmental and cellular cues to succeed in fertilization, and this process relies heavily on ion channels. New observations bring to light the relevant participation of Cl − channels and anion transporters in some of the main sperm functions. Here we review the evidence that indicates the participation of Cl − channels in motility, maturation, and the acrosome reaction (AR), and what is known about their molecular identity and regulation. Our better understanding of sperm anion transport will yield tools to handle some infertility problems, improve animal breeding and preserve biodiversity, and develop selective and secure male contraceptives.

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Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization

Cited by 213 publications

References 48 publications

A polycystin-1 controls postcopulatory reproductive selection in mice

A polycystin-1 controls postcopulatory reproductive selection in mice

Tissue-specific PKA inhibition using a chemical genetic approach and its application to studies on sperm capacitation

Cl− Channels and Transporters in Sperm Physiology

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