EFCAB9 通过感知生理 pH 值和钙来调节精子活力。
Dual Sensing of Physiologic pH and Calcium by EFCAB9 Regulates Sperm Motility.
机构信息
Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
出版信息
Cell. 2019 May 30;177(6):1480-1494.e19. doi: 10.1016/j.cell.2019.03.047. Epub 2019 May 2.
Varying pH of luminal fluid along the female reproductive tract is a physiological cue that modulates sperm motility. CatSper is a sperm-specific, pH-sensitive calcium channel essential for hyperactivated motility and male fertility. Multi-subunit CatSper channel complexes organize linear Ca signaling nanodomains along the sperm tail. Here, we identify EF-hand calcium-binding domain-containing protein 9 (EFCAB9) as a bifunctional, cytoplasmic machine modulating the channel activity and the domain organization of CatSper. Knockout mice studies demonstrate that EFCAB9, in complex with the CatSper subunit, CATSPERζ, is essential for pH-dependent and Ca-sensitive activation of the CatSper channel. In the absence of EFCAB9, sperm motility and fertility is compromised, and the linear arrangement of the Ca signaling domains is disrupted. EFCAB9 interacts directly with CATSPERζ in a Ca-dependent manner and dissociates at elevated pH. These observations suggest that EFCAB9 is a long-sought, intracellular, pH-dependent Ca sensor that triggers changes in sperm motility.
女性生殖道内的腔液 pH 值变化是调节精子运动的生理信号。CatSper 是一种精子特异性、pH 敏感的钙通道，对精子的超激活运动和雄性生育力至关重要。多亚基 CatSper 通道复合物沿精子尾部组织线性 Ca 信号纳米域。在这里，我们鉴定出 EF 手钙离子结合域蛋白 9（EFCAB9）作为一种双功能的细胞质机器，调节 CatSper 通道的活性和结构域组织。敲除小鼠研究表明，EFCAB9 与 CatSper 亚基 CATSPERζ 形成复合物，对于 CatSper 通道的 pH 依赖性和 Ca 敏感性激活是必不可少的。在缺乏 EFCAB9 的情况下，精子运动和生育能力受损，Ca 信号域的线性排列被破坏。EFCAB9 以 Ca 依赖性方式与 CATSPERζ 直接相互作用，并在 pH 值升高时解离。这些观察结果表明，EFCAB9 是一种长期以来被寻找的、细胞内的、pH 依赖性的 Ca 传感器，它触发精子运动的变化。
Zotero 插件