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Publication : The significance of electrical signals in maturing spermatozoa for phosphoinositide regulation through voltage-sensing phosphatase.

First Author  Kawai T Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  7289
PubMed ID  39181879 Mgi Jnum  J:359008
Mgi Id  MGI:7713829 Doi  10.1038/s41467-024-51755-2
Citation  Kawai T, et al. (2024) The significance of electrical signals in maturing spermatozoa for phosphoinositide regulation through voltage-sensing phosphatase. Nat Commun 15(1):7289
abstractText  Voltage-sensing phosphatase (VSP) exhibits voltage-dependent phosphatase activity toward phosphoinositides. VSP generates a specialized phosphoinositide environment in mammalian sperm flagellum. However, the voltage-sensing mechanism of VSP in spermatozoa is not yet characterized. Here, we found that VSP is activated during sperm maturation, indicating that electric signals in immature spermatozoa are essential. Using a heterologous expression system, we show the voltage-sensing property of mouse VSP (mVSP). The voltage-sensing threshold of mVSP is approximately -30 mV, which is sensitive enough to activate mVSP in immature spermatozoa. We also report several knock-in mice in which we manipulate the voltage-sensitivity or electrochemical coupling of mVSP. Notably, the V312R mutant, with a minor voltage-sensitivity change, exhibits abnormal sperm motility after, but not before, capacitation. Additionally, the V312R mutant shows a significant change in the acyl-chain profile of phosphoinositide. Our findings suggest that electrical signals during sperm maturation are crucial for establishing the optimal phosphoinositide environment in spermatozoa.
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