由电压感应磷酸酶（VSP）介导的极化 PtdIns(4,5)P 分布调节精子运动。
Polarized PtdIns(4,5)P distribution mediated by a voltage-sensing phosphatase (VSP) regulates sperm motility.
机构信息
Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
出版信息
Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):26020-26028. doi: 10.1073/pnas.1916867116. Epub 2019 Nov 27.
The voltage-sensing phosphatase (VSP) is a unique protein that shows voltage-dependent phosphoinositide phosphatase activity. Here we report that VSP is activated in mice sperm flagellum and generates a unique subcellular distribution pattern of PtdIns(4,5)P Sperm from VSP mice show more Ca influx upon capacitation than VSP mice and abnormal circular motion. VSP-deficient sperm showed enhanced activity of Slo3, a PtdIns(4,5)P-sensitive K channel, which selectively localizes to the principal piece of the flagellum and indirectly enhances Ca influx. Most interestingly, freeze-fracture electron microscopy analysis indicates that normal sperm have much less PtdIns(4,5)P in the principal piece than in the midpiece of the flagellum, and this polarized PtdIns(4,5)P distribution disappeared in VSP-deficient sperm. Thus, VSP appears to optimize PtdIns(4,5)P distribution of the principal piece. These results imply that flagellar PtdIns(4,5)P distribution plays important roles in ion channel regulation as well as sperm motility.
电压感应磷酸酶（VSP）是一种具有电压依赖性磷酸肌醇磷酸酶活性的独特蛋白。本文报道 VSP 在小鼠精子鞭毛中被激活，并产生独特的 PtdIns(4,5)P 分布模式。VSP 敲除小鼠的精子在获能后表现出更多的 Ca2+内流和异常的圆周运动。VSP 缺失的精子中 Slo3 （一种 PtdIns(4,5)P 敏感的 K 通道）的活性增强，该通道选择性地定位于鞭毛的主段，并间接增强 Ca2+内流。最有趣的是，冷冻断裂电子显微镜分析表明，正常精子的主段中 PtdIns(4,5)P 的含量明显低于中段，而 VSP 缺失的精子中这种极化的 PtdIns(4,5)P 分布消失了。因此，VSP 似乎优化了主段中的 PtdIns(4,5)P 分布。这些结果表明，鞭毛 PtdIns(4,5)P 的分布在离子通道调节以及精子运动中起着重要作用。
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