02364nas a2200253   4500008004100000245008100041210006900122260001600191520146600207100002001673700001701693700003001710700003201740700002201772700002001794700002301814700002201837700002001859700001701879700001701896700002101913700002301934856015301957       2013                        ENG d00aCompartmentalization of Distinct cAMP Signaling Pathways in Mammalian Sperm.0 aCompartmentalization of Distinct cAMP Signaling Pathways in Mamm  c2013 Oct 153 a<p>Fertilization competence is acquired in the female tract in a process known as capacitation. Capacitation is needed for the activation of motility (e.g. hyperactivation) and to prepare the sperm for an exocytotic process known as acrosome reaction. While the HCO(3)--dependent soluble adenylyl cyclase Adcy10 plays a role in motility, less is known about the source of cAMP in the sperm head. Transmembrane adenylyl cyclases (tmACs) are another possible source of cAMP. These enzymes are regulated by stimulatory heterotrimeric Gs proteins; however, the presence of Gs or tmACs in mammalian sperm has been controversial. In this manuscript, we used Western blotting and cholera toxin-dependent ADP ribosylation to show Gs presence in the sperm head. Also, we showed that forskolin, a tmAC specific activator, induces cAMP accumulation in sperm from both WT and Adcy10 null mice. This increase is blocked by the tmAC inhibitor SQ-22536 but not by the Adcy10 inhibitor KH7. While Gs immunoreactivity and tmAC activity are detected in the sperm head, PKA is only found in the tail, where Adcy10 was previously shown to reside. Consistent with an acrosomal localization, Gs reactivity is lost in acrosome reacted sperm, and forskolin is able to increase intracellular Ca(2+) and induce the acrosome reaction. Altogether, these data suggest that cAMP pathways are compartmentalized in sperm, with Gs and tmAC in the head and Adcy10 and PKA in the flagellum.</p>
1 aWertheimer, Eva1 aKrapf, Dario1 aVega-Beltran, José, Luis1 aSánchez-Cárdenas, Claudia1 aNavarrete, Felipe1 aHaddad, Douglas1 aEscoffier, Jessica1 aSalicioni, Ana, M1 aLevin, Lonny, R1 aBuck, Jochen1 aMager, Jesse1 aDarszon, Alberto1 aVisconti, Pablo, E  uhttps://www.umass.edu/veterinary-animal-sciences/research-faculty/publications/compartmentalization-of-distinct-camp-signaling-pathways-in-mammalian