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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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487327 | PMC |
| http://dx.doi.org/10.3389/fcell.2020.572735 | DOI Listing |
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