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Publication : Molecular Mechanism Underlying the Action of <i>Zona-pellucida</i> Glycoproteins on Mouse Sperm.

First Author  Balbach M Year  2020
Journal  Front Cell Dev Biol Volume  8
Pages  572735 PubMed ID  32984353
Mgi Jnum  J:298992 Mgi Id  MGI:6489638
Doi  10.3389/fcell.2020.572735 Citation  Balbach M, et al. (2020) Molecular Mechanism Underlying the Action of Zona-pellucida Glycoproteins on Mouse Sperm. Front Cell Dev Biol 8:572735
abstractText  Mammalian oocytes are enveloped by the zona pellucida (ZP), an extracellular matrix of glycoproteins. In sperm, stimulation with ZP proteins evokes a rapid Ca(2+) influx via the sperm-specific, pH-sensitive Ca(2+) channel CatSper. However, the physiological role and molecular mechanisms underlying ZP-dependent activation of CatSper are unknown. Here, we delineate the sequence of ZP-signaling events in mouse sperm. We show that ZP proteins evoke a rapid intracellular pH i increase that rests predominantly on Na(+)/H(+) exchange by NHA1 and requires cAMP synthesis by the soluble adenylyl cyclase sAC as well as a sufficiently negative membrane potential set by the spem-specific K(+) channel Slo3. The alkaline-activated CatSper channel translates the ZP-induced pH i increase into a Ca(2+) response. Our findings reveal the molecular components underlying ZP action on mouse sperm, opening up new avenues for understanding the basic principles of sperm function and, thereby, mammalian fertilization.
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