| Literature DB >> 31776261 |
Takafumi Kawai1, Haruhiko Miyata2, Hiroki Nakanishi3, Souhei Sakata1, Shin Morioka4,5, Junko Sasaki4,6, Masahiko Watanabe7, Kenji Sakimura8, Toyoshi Fujimoto9, Takehiko Sasaki4,6, Masahito Ikawa2, Yasushi Okamura10,11.
Abstract
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)P2 Sperm from VSP-/- mice show more Ca2+ influx upon capacitation than VSP+/- mice and abnormal circular motion. VSP-deficient sperm showed enhanced activity of Slo3, a PtdIns(4,5)P2-sensitive K+ channel, which selectively localizes to the principal piece of the flagellum and indirectly enhances Ca2+ influx. Most interestingly, freeze-fracture electron microscopy analysis indicates that normal sperm have much less PtdIns(4,5)P2 in the principal piece than in the midpiece of the flagellum, and this polarized PtdIns(4,5)P2 distribution disappeared in VSP-deficient sperm. Thus, VSP appears to optimize PtdIns(4,5)P2 distribution of the principal piece. These results imply that flagellar PtdIns(4,5)P2 distribution plays important roles in ion channel regulation as well as sperm motility.Entities:
Keywords: PtdIns(4,5)P2; membrane potential; sperm; voltage-sensing phosphatase
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Year: 2019 PMID： 31776261 PMCID： PMC6925991 DOI： 10.1073/pnas.1916867116
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205