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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Sperm-specific protein kinase A catalytic subunit C alpha(2) orchestrates cAMP signaling for male fertility
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Sperm-specific protein kinase A catalytic subunit C alpha(2) orchestrates cAMP signaling for male fertility

机译:精子特异性蛋白激酶A催化亚基C alpha(2)协调雄性育性的cAMP信号传导

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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 Calpha(2) or C-s. We generated mice that lack Calpha(2) to determine its importance in the events downstream of cAMP production. Male Calpha(2) null mice produce normal numbers of sperm that swim spontaneously in vitro. Thus, Calpha(2) has no required role in formation of a functional flagellum or the initiation of motility. in contrast, we find that Calpha(2) is required for bicarbonate to speed the flagellar beat and facilitate Ca2+ entry channels. In addition, Calpha(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, Calpha(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.
机译:一个异常的cAMP信号系统介导了许多使精子与卵子接触的事件。它的成分包括非典型的,经碳酸氢盐刺激的精子腺苷酸环化酶和cAMP依赖性蛋白激酶(PKA),其独特的催化亚基称为Calpha(2)或C-s。我们生成了缺少Calpha(2)的小鼠来确定其在cAMP产生下游事件中的重要性。雄性Calpha(2)空小鼠产生正常数量的精子,这些精子在体外自发游泳。因此,Calpha(2)在功能性鞭毛的形成或运动性的启动中没有必需的作用。相反,我们发现碳酸氢盐需要Calpha(2)来加速鞭毛搏动并促进Ca2 +进入通道。此外,Calpha(2)对于精子成熟序列后期发生的蛋白质酪氨酸磷酸化和cAMP产生的负反馈控制是必需的,此处显示。与几个重要的精子功能中的这些特定的缺陷一致,尽管正常的交配行为,Calpha(2)空男性是不育的。这些结果定义了PKA在精子细胞生物学中的几个关键作用,将已知和独特的PKA介导的事件整合在一起,这些事件对于男性生育是必需的。

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