Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA.
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 5650871, Japan.
Cell Rep. 2022 Jan 18;38(3):110226. doi: 10.1016/j.celrep.2021.110226. Epub 2022 Jan 7.
In mammalian sperm cells, regulation of spatiotemporal Ca signaling relies on the quadrilinear Ca signaling nanodomains in the flagellar membrane. The sperm-specific, multi-subunit CatSper Ca channel, which is crucial for sperm hyperactivated motility and male fertility, organizes the nanodomains. Here, we report CatSperτ, the C2cd6-encoded membrane-associating C2 domain protein, can independently migrate to the flagella and serve as a major targeting component of the CatSper channel complex. CatSperτ loss of function in mice demonstrates that it is essential for sperm hyperactivated motility and male fertility. CatSperτ targets the CatSper channel into the quadrilinear nanodomains in the flagella of developing spermatids, whereas it is dispensable for functional channel assembly. CatSperτ interacts with ciliary trafficking machinery in a C2-dependent manner. These findings provide insights into the CatSper channel trafficking to the Ca signaling nanodomains and the shared molecular mechanisms of ciliary and flagellar membrane targeting.
在哺乳动物精子细胞中，时空 Ca 信号的调节依赖于鞭毛膜中的四线性 Ca 信号纳米域。精子特异性的多亚基 CatSper Ca 通道对于精子超激活运动和男性生育能力至关重要，它组织了纳米域。在这里，我们报告了 CatSperτ，即 C2cd6 编码的膜相关 C2 结构域蛋白，它可以独立迁移到鞭毛，并作为 CatSper 通道复合物的主要靶向成分。CatSperτ 在小鼠中的功能丧失表明它对于精子超激活运动和男性生育能力是必不可少的。CatSperτ 将 CatSper 通道靶向到发育中的精母细胞鞭毛中的四线性纳米域，而对于功能性通道组装则是可有可无的。CatSperτ 以 C2 依赖的方式与纤毛运输机制相互作用。这些发现为 CatSper 通道向 Ca 信号纳米域的运输以及纤毛和鞭毛膜靶向的共享分子机制提供了深入了解。
