A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa.

A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa.
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DOI:
10.1038/ncomms1153
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发表时间:
2011-01-11
影响因子:
16.6
通讯作者:
Clapham DE
Clapham DE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chung JJ;Navarro B;Krapivinsky G;Krapivinsky L;Clapham DE

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钙信号是成功受精的关键。在精子中,获能、运动过度激活和顶体反应都是由细胞内Ca 2+的增加介导的。精子蛋白的阳离子通道(CATSPERS 1 -4)形成精子的超活化运动性和男性生育力所需的碱化激活的Ca 2+选择性通道。每个CatSper 1 -4基因编码围绕Ca 2+选择性孔的四聚体的亚基,类似于其他六跨膜离子通道α亚基。除了成孔蛋白外,精子Ca 2+通道还含有辅助亚基CATSPERβ和CATSPERγ。在这里,我们确定Tmem 146基因产物作为一个新的亚基,CATSPERδ,所需的CATSPER通道功能。我们发现,缺乏精子尾部特异性CATSPERδ的小鼠是不育的,它们的精子缺乏钙电流和超活化运动。我们表明,CATSPERδ是CATSPER通道复合物的基本要素,并建议CATSPERδ是正确的CATSPER通道组装和/或运输所必需的。
Calcium signaling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility, and the acrosome reaction are all mediated by increases in intracellular Ca2+. Cation channels of sperm proteins (CATSPERS1-4) form an alkalinization-activated Ca2+-selective channel required for the hyperactivated motility of spermatozoa and male fertility. Each of the CatSper1-4 genes encodes a subunit of a tetramer surrounding a Ca2+-selective pore, in analogy with other six-transmembrane ion channel α subunits. In addition to the pore-forming proteins, the sperm Ca2+ channel contains auxiliary subunits, CATSPERβ and CATSPERγ. Here, we identify the Tmem146 gene product as a novel subunit, CATSPERδ, required for CATSPER channel function. We find that mice lacking the sperm tail-specific CATSPERδ are infertile and their spermatozoa lack both Ca2+ current and hyperactivated motility. We show that CATSPERδ is an essential element of the CATSPER channel complex and propose that CATSPERδ is required for proper CATSPER channel assembly and/or transport.
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