Title | The "soluble" adenylyl cyclase in sperm mediates multiple signaling events required for fertilization. |
Publication Type | Journal Article |
Year of Publication | 2005 |
Authors | Hess KC, Jones BH, Marquez B, Chen Y, Ord TS, Kamenetsky M, Miyamoto C, Zippin JH, Kopf GS, Suarez SS, Levin LR, Williams CJ, Buck J, Moss SB |
Journal | Dev Cell |
Volume | 9 |
Issue | 2 |
Pagination | 249-59 |
Date Published | 2005 Aug |
ISSN | 1534-5807 |
Keywords | Acrosome, Adenylyl Cyclase Inhibitors, Adenylyl Cyclases, Animals, Cyclic AMP, Exocytosis, Fertilization, Male, Mice, Mice, Knockout, Phosphorylation, Signal Transduction, Solubility, Sperm Capacitation, Sperm Motility, Spermatozoa, Tyrosine |
Abstract | Mammalian fertilization is dependent upon a series of bicarbonate-induced, cAMP-dependent processes sperm undergo as they "capacitate," i.e., acquire the ability to fertilize eggs. Male mice lacking the bicarbonate- and calcium-responsive soluble adenylyl cyclase (sAC), the predominant source of cAMP in male germ cells, are infertile, as the sperm are immotile. Membrane-permeable cAMP analogs are reported to rescue the motility defect, but we now show that these "rescued" null sperm were not hyperactive, displayed flagellar angulation, and remained unable to fertilize eggs in vitro. These deficits uncover a requirement for sAC during spermatogenesis and/or epididymal maturation and reveal limitations inherent in studying sAC function using knockout mice. To circumvent this restriction, we identified a specific sAC inhibitor that allowed temporal control over sAC activity. This inhibitor revealed that capacitation is defined by separable events: induction of protein tyrosine phosphorylation and motility are sAC dependent while acrosomal exocytosis is not dependent on sAC. |
DOI | 10.1016/j.devcel.2005.06.007 |
Alternate Journal | Dev. Cell |
PubMed ID | 16054031 |
PubMed Central ID | PMC3082461 |
Grant List | HD044740 / HD / NICHD NIH HHS / United States NIH HD42060 / HD / NICHD NIH HHS / United States HD38722 / HD / NICHD NIH HHS / United States R01 HD038722 / HD / NICHD NIH HHS / United States R01 HD044740 / HD / NICHD NIH HHS / United States F31 HD043693 / HD / NICHD NIH HHS / United States R01 GM062328 / GM / NIGMS NIH HHS / United States R01 HD038722-04 / HD / NICHD NIH HHS / United States R01 HD038722-02 / HD / NICHD NIH HHS / United States R01 HD059913-02 / HD / NICHD NIH HHS / United States R01 HD059913-01 / HD / NICHD NIH HHS / United States R01 HD038722-01A1 / HD / NICHD NIH HHS / United States R01 HD059913-03 / HD / NICHD NIH HHS / United States R01 HD038722-03 / HD / NICHD NIH HHS / United States R01 HD059913 / HD / NICHD NIH HHS / United States GM62328 / GM / NIGMS NIH HHS / United States 5 F31 HD43693 / HD / NICHD NIH HHS / United States |