Sperm-specific protein kinase A catalytic subunit Cα 2 orchestrates cAMP signaling for male fertility
- 31 August 2004
- journal article
- Published by National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (37) , 13483-13488
Abstract
An unusual cAMP signaling system mediates many of the events that prepare spermatozoa to meet the egg. Its components include the atypical, bicarbonate-stimulated, sperm adenylyl cyclase and a cAMP-dependent protein kinase (PKA) with the unique catalytic subunit termed Cα 2 or C s . We generated mice that lack Cα 2 to determine its importance in the events downstream of cAMP production. Male Cα 2 null mice produce normal numbers of sperm that swim spontaneously in vitro . Thus, Cα 2 has no required role in formation of a functional flagellum or the initiation of motility. In contrast, we find that Cα 2 is required for bicarbonate to speed the flagellar beat and facilitate Ca 2+ entry channels. In addition, Cα 2 is needed for the protein tyrosine phosphorylation that occurs late in the sequence of sperm maturation and for a negative feedback control of cAMP production, revealed here. Consistent with these specific defects in several important sperm functions, Cα 2 null males are infertile despite normal mating behavior. These results define several crucial roles of PKA in sperm cell biology, bringing together both known and unique PKA-mediated events that are necessary for male fertility.Keywords
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