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Publication : The "soluble" adenylyl cyclase in sperm mediates multiple signaling events required for fertilization.

First Author  Hess KC Year  2005
Journal  Dev Cell Volume  9
Issue  2 Pages  249-59
PubMed ID  16054031 Mgi Jnum  J:100583
Mgi Id  MGI:3588903 Doi  10.1016/j.devcel.2005.06.007
Citation  Hess KC, et al. (2005) The 'soluble' adenylyl cyclase in sperm mediates multiple signaling events required for fertilization. Dev Cell 9(2):249-59
abstractText  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.
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