期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2019
卷号:116
期号:51
页码:26020-26028
DOI:10.1073/pnas.1916867116
出版社:The National Academy of Sciences of the United States of America
摘要: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 2 . Sperm from VSP −/− mice show more Ca 2+ influx upon capacitation than VSP +/− mice and abnormal circular motion. VSP-deficient sperm showed enhanced activity of Slo3, a PtdIns(4,5)P 2 -sensitive K + channel, which selectively localizes to the principal piece of the flagellum and indirectly enhances Ca 2+ influx. Most interestingly, freeze-fracture electron microscopy analysis indicates that normal sperm have much less PtdIns(4,5)P 2 in the principal piece than in the midpiece of the flagellum, and this polarized PtdIns(4,5)P 2 distribution disappeared in VSP-deficient sperm. Thus, VSP appears to optimize PtdIns(4,5)P 2 distribution of the principal piece. These results imply that flagellar PtdIns(4,5)P 2 distribution plays important roles in ion channel regulation as well as sperm motility..