Huang Xiaofang, Miyata Haruhiko, Wang Huafeng, Mori Giulia, Iida-Norita Rie, Ikawa Masahito, Percudani Riccardo, Chung Jean-Ju
Department of Cellular and Molecular Physiology, Yale School of Medicine, Yale University, New Haven, CT, 06510, USA.
Research Institute for Microbial Diseases, Osaka University, Suita 5650871, Japan.
bioRxiv. 2023 Mar 17:2023.03.17.532952. doi: 10.1101/2023.03.17.532952.
Calcium signaling is critical for successful fertilization. In spermatozoa, calcium influx into the sperm flagella mediated by the sperm specific CatSper calcium channel is necessary for hyperactivated motility and male fertility. CatSper is a macromolecular complex and is repeatedly arranged in zigzag rows within four linear nanodomains along the sperm flagella. Here, we report that the -encoded transmembrane domain containing protein, CATSPERθ, is essential for the CatSper channel assembly during sperm tail formation. CATSPERθ facilitates the channel assembly by serving as a scaffold for a pore forming subunit CATSPER4. CATSPERθ is specifically localized at the interface of a CatSper dimer and can self-interact, suggesting its potential role in CatSper dimer formation. Male mice lacking CATSPERθ are infertile because the sperm lack the entire CatSper channel from sperm flagella, rendering sperm unable to hyperactivate, regardless of their normal expression in the testis. In contrast, genetic abrogation of any of the other CatSper transmembrane subunits results in loss of CATSPERθ protein in the spermatid cells during spermatogenesis. CATSPERθ might acts as a checkpoint for the properly assembled CatSper channel complex to traffic to sperm flagella. This study provides insights into the CatSper channel assembly and elucidates the physiological role of CATSPERθ in sperm motility and male fertility.
钙信号对于成功受精至关重要。在精子中，由精子特异性CatSper钙通道介导的钙离子流入精子鞭毛对于超活化运动和雄性生育能力是必需的。CatSper是一种大分子复合物，沿着精子鞭毛在四个线性纳米域内呈锯齿状排列。在此，我们报告，由 编码的含跨膜结构域蛋白CATSPERθ在精子尾部形成过程中对CatSper通道组装至关重要。CATSPERθ通过作为孔形成亚基CATSPER4的支架来促进通道组装。CATSPERθ特异性定位于CatSper二聚体的界面，并且可以自我相互作用，这表明其在CatSper二聚体形成中的潜在作用。缺乏CATSPERθ的雄性小鼠不育，因为精子从精子鞭毛中缺乏整个CatSper通道，导致精子无法超活化，尽管它们在睾丸中正常表达。相反，任何其他CatSper跨膜亚基的基因敲除都会导致精子发生过程中精子细胞中CATSPERθ蛋白的缺失。CATSPERθ可能作为正确组装的CatSper通道复合物运输到精子鞭毛的一个检查点。这项研究为CatSper通道组装提供了见解，并阐明了CATSPERθ在精子运动和雄性生育能力中的生理作用。
