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Molecular mechanism underlying the action of zona-pellucida glycoproteins on Mouse Sperm

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Balbach,  Melanie
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

Hamzeh,  Hussein
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Kaupp,  Ulrich Benjamin
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Citation

Balbach, M., Hamzeh, H., Jikeli, J. F., Brenker, C., Schiffer, C., Hansen, J. N., et al. (2020). Molecular mechanism underlying the action of zona-pellucida glycoproteins on Mouse Sperm. Frontiers in Cell and Developmental Biology, 8: 572735. doi:10.3389/fcell.2020.572735.


Cite as: https://hdl.handle.net/21.11116/0000-0008-5509-F
Abstract
Mammalian oocytes are enveloped by the zona pellucida (ZP), an extracellular matrix of glycoproteins. In sperm, stimulation with ZP proteins evokes a rapid Ca2+ influx via the sperm-specific, pH-sensitive Ca2+ 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 Ca2+ 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.