All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility
All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility
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DOI：
10.1073/pnas.0610286104
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发表时间：
2007-01-23
影响因子：
11.1
通讯作者：
Clapham, David E.
中科院分区：
文献类型：
--
作者：
Qi, Huayu;Moran, Magdalene M.;Clapham, David E.
哺乳动物的精子在射精时可以活动，但在它们能够使卵子受精之前，它们必须获得更多的推力才能穿过卵丘和透明带。过度激活的精子的强烈不对称运动需要通过碱化激活的电压敏感钙选择电流(I-CatSper)进入精子尾部。超激活需要可能的离子通道基因CatSper1和CatSper2，但另外两个相关基因(CatSper3和CatSper4)的功能尚不清楚。在这里，我们发现，靶向阻断小鼠CatSper3或CatSper4也可以抑制I-CatSper，精子细胞过度激活的活力和男性生育能力，但不影响精子发生或初始活力。CatSper之间的直接蛋白质相互作用，这些蛋白质的精子特异性，以及I-CatSper在四只CatSper(-/-)小鼠中的缺失，表明CatSpers是高度专门化的鞭毛蛋白。
Mammalian spermatozoa become motile at ejaculation, but before they can fertilize the egg, they must acquire more thrust to penetrate the cumulus and zona pellucida. The forceful asymmetric motion of hyperactivated spermatozoa requires Ca2+ entry into the sperm tail by an alkalinization-activated voltage-sensitive Ca2+-selective current (I-CatSper). Hyperactivation requires CatSper1 and CatSper2 putative ion channel genes, but the function of two other related genes (CatSper3 and CatSper4) is not known. Here we show that targeted disruption of murine CatSper3 or CatSper4 also abrogated I-CatSper, sperm cell hyperactivated motility and male fertility but did not affect spermatogenesis or initial motility. Direct protein interactions among CatSpers, the sperm specificity of these proteins, and loss of I-CatSper in each of the four CatSper(-/-) mice indicate that CatSpers are highly specialized flagellar proteins.