Molecular Mechanism Underlying the Action of Zona-pellucida 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 2+ influx via the sperm-specific, pH-sensitive Ca 2+ channel CatSper. However, the physiological role and molecular mechanisms underlying ZP-...

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Published in:Frontiers in cell and developmental biology 2020-08, Vol.8, p.572735-572735
Main Authors: Balbach, Melanie, Hamzeh, Hussein, Jikeli, Jan F., Brenker, Christoph, Schiffer, Christian, Hansen, Jan N., Neugebauer, Pia, Trötschel, Christian, Jovine, Luca, Han, Ling, Florman, Harvey M., Kaupp, U. Benjamin, Strünker, Timo, Wachten, Dagmar
Format: Article
Language:English
Subjects:
calcium
Cell and Developmental Biology
Medicin och hälsovetenskap
mouse sperm
sodium-proton exchange
sperm motility
zona pellucida
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Summary: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.
ISSN:2296-634X
2296-634X
DOI:10.3389/fcell.2020.572735