Polarized PtdIns(4,5)P₂ distribution mediated by a voltage-sensing phosphatase (VSP) regulates sperm motility

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+ i...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2019-12, Vol.116 (51), p.26020-26028
Main Authors: Kawai, Takafumi, Miyata, Haruhiko, Nakanishi, Hiroki, Sakata, Souhei, Morioka, Shin, Sasaki, Junko, Watanabe, Masahiko, Sakimura, Kenji, Fujimoto, Toyoshi, Sasaki, Takehiko, Ikawa, Masahito, Okamura, Yasushi
Format: Article
Language:English
Subjects:
Biological Sciences
Calcium influx
Calcium ions
Capacitation
Electric potential
Electron microscopy
Flagella
Freeze-fracture
Ion channels
Motility
Phosphatase
Phosphatidylinositol 4,5-diphosphate
Potassium channels
Sperm
Voltage
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1916867116