Molecular Mechanism Underlying the Action of Glycoproteins on Mouse Sperm.

Mammalian oocytes are enveloped by the zona pellucida (ZP), an extracellular matrix of glycoproteins. In sperm, stimulation with ZP proteins evokes a rapid Ca influx via the sperm-specific, pH-sensitive Ca 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 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 increase into a Ca 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.

Copyright © 2020 Balbach, Hamzeh, Jikeli, Brenker, Schiffer, Hansen, Neugebauer, Trötschel, Jovine, Han, Florman, Kaupp, Strünker and Wachten.

PMID: 32984353