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

Takafumi Kawai; Haruhiko Miyata; Hiroki Nakanishi; Souhei Sakata; Shin Morioka; Junko Sasaki; Masahiko Watanabe; Kenji Sakimura; Toyoshi Fujimoto; Takehiko Sasaki; Masahito Ikawa; Yasushi Okamura

doi:10.1073/pnas.1916867116

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

Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):26020-26028. doi: 10.1073/pnas.1916867116. Epub 2019 Nov 27.

Authors

Takafumi Kawai¹, Haruhiko Miyata², Hiroki Nakanishi³, Souhei Sakata¹, Shin Morioka^{4

5}, Junko Sasaki^{4

6}, Masahiko Watanabe⁷, Kenji Sakimura⁸, Toyoshi Fujimoto⁹, Takehiko Sasaki^{4

6}, Masahito Ikawa², Yasushi Okamura^{10

11}

Affiliations

¹ Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
² Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
³ Research Center for Biosignal, Akita University, Akita 010-8543, Japan.
⁴ Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
⁵ Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
⁶ Graduate School of Medicine, Akita University, Akita 010-8543, Japan.
⁷ Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
⁸ Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
⁹ Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan.
¹⁰ Graduate School of Medicine, Osaka University, Suita 565-0871, Japan; yokamura@phys2.med.osaka-u.ac.jp.
¹¹ Graduate School of Frontier Bioscience, Osaka University, Suita 565-0871, Japan.

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.

Keywords: PtdIns(4,5)P2; membrane potential; sperm; voltage-sensing phosphatase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium Channels / metabolism
Flagella / metabolism
Ion Channels / metabolism*
Large-Conductance Calcium-Activated Potassium Channels / metabolism
Male
Membrane Potentials / physiology
Mice
Mice, Knockout
Phosphatidylinositol 4,5-Diphosphate / chemistry*
Phosphatidylinositol 4,5-Diphosphate / metabolism*
Phosphoric Monoester Hydrolases / genetics
Phosphoric Monoester Hydrolases / metabolism*
Sperm Motility / physiology*
Sperm Tail / metabolism
Spermatozoa / metabolism

Substances

Calcium Channels
Ion Channels
Kcnu1 protein, mouse
Large-Conductance Calcium-Activated Potassium Channels
Phosphatidylinositol 4,5-Diphosphate
Phosphoric Monoester Hydrolases