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Publication : Polarized PtdIns(4,5)P<sub>2</sub> distribution mediated by a voltage-sensing phosphatase (VSP) regulates sperm motility.

First Author  Kawai T Year  2019
Journal  Proc Natl Acad Sci U S A Volume  116
Issue  51 Pages  26020-26028
PubMed ID  31776261 Mgi Jnum  J:282803
Mgi Id  MGI:6383235 Doi  10.1073/pnas.1916867116
Citation  Kawai T, et al. (2019) Polarized PtdIns(4,5)P2 distribution mediated by a voltage-sensing phosphatase (VSP) regulates sperm motility. Proc Natl Acad Sci U S A 116(51):26020-26028
abstractText  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 Ca(2+) 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 Ca(2+) 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.
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