期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：37
页码：13483-13488
DOI：10.1073/pnas.0405580101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 C{alpha}2 or Cs. We generated mice that lack C{alpha}2 to determine its importance in the events downstream of cAMP production. Male C{alpha}2 null mice produce normal numbers of sperm that swim spontaneously in vitro. Thus, C{alpha}2 has no required role in formation of a functional flagellum or the initiation of motility. In contrast, we find that C{alpha}2 is required for bicarbonate to speed the flagellar beat and facilitate Ca2+ entry channels. In addition, C{alpha}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, C{alpha}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.
