Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell Rep. 2018 Sep 4;24(10):2606-2613. doi: 10.1016/j.celrep.2018.08.016.
Ion channels control sperm navigation within the female reproductive tract and, thus, are critical for their ability to find and fertilize an egg. The flagellar calcium channel CatSper controls sperm hyperactivated motility and is dependent on an alkaline cytoplasmic pH. The latter is accomplished by either proton transporters or, in human sperm, via the voltage-gated proton channel Hv1. To provide concerted regulation, ion channels and their regulatory proteins must be compartmentalized. Here, we describe flagellar regulatory nanodomains comprised of Hv1, CatSper, and its regulatory protein ABHD2. Super-resolution microscopy revealed that Hv1 is distributed asymmetrically within bilateral longitudinal lines and that inhibition of this channel leads to a decrease in sperm rotation along the long axis. We suggest that specific distribution of flagellar nanodomains provides a structural basis for the selective activation of CatSper and subsequent flagellar rotation. The latter, together with hyperactivated motility, enhances the fertility of sperm.
离子通道控制精子在雌性生殖道内的导航，因此对于它们寻找和受精卵子的能力至关重要。鞭毛钙通道 CatSper 控制精子超激活运动，并依赖于碱性细胞质 pH 值。后者通过质子转运体或在人类精子中通过电压门控质子通道 Hv1 来实现。为了提供协调的调节，离子通道及其调节蛋白必须进行区室化。在这里，我们描述了由 Hv1、CatSper 和其调节蛋白 ABHD2 组成的鞭毛调节纳米域。超分辨率显微镜显示，Hv1 在双侧纵向线上呈不对称分布，并且该通道的抑制导致精子沿长轴的旋转减少。我们认为，鞭毛纳米域的特定分布为 CatSper 的选择性激活以及随后的鞭毛旋转提供了结构基础。后者与超激活运动一起，提高了精子的生育能力。
