Molecular Mechanism Underlying the Action of Zona-pellucida Glycoproteins on Mouse Sperm

Melanie Balbach; Hussein Hamzeh; Jan F. Jikeli; Christoph Brenker; Christian Schiffer; Jan N. Hansen; Pia Neugebauer; Christian Trötschel; Luca Jovine; Ling Han; Harvey M. Florman; U. Benjamin Kaupp; U. Benjamin Kaupp; Timo Strünker; Dagmar Wachten

doi:10.3389/fcell.2020.572735

Frontiers in Cell and Developmental Biology (Aug 2020)

Molecular Mechanism Underlying the Action of Zona-pellucida Glycoproteins on Mouse Sperm

Melanie Balbach,
Hussein Hamzeh,
Jan F. Jikeli,
Christoph Brenker,
Christian Schiffer,
Jan N. Hansen,
Pia Neugebauer,
Christian Trötschel,
Luca Jovine,
Ling Han,
Harvey M. Florman,
U. Benjamin Kaupp,
U. Benjamin Kaupp,
Timo Strünker,
Dagmar Wachten

Affiliations

Melanie Balbach: Center of Advanced European Studies and Research, Department of Molecular Sensory Systems, Bonn, Germany
Hussein Hamzeh: Center of Advanced European Studies and Research, Department of Molecular Sensory Systems, Bonn, Germany
Jan F. Jikeli: Institute of Innate Immunity, Department of Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, Germany
Christoph Brenker: Center of Reproductive Medicine and Andrology, University Hospital Münster, University of Münster, Münster, Germany
Christian Schiffer: Center of Reproductive Medicine and Andrology, University Hospital Münster, University of Münster, Münster, Germany
Jan N. Hansen: Institute of Innate Immunity, Department of Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, Germany
Pia Neugebauer: Institute of Innate Immunity, Department of Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, Germany
Christian Trötschel: Biochemie der Pflanzen, Ruhr-Universität Bochum, Bochum, Germany
Luca Jovine: Department of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden
Ling Han: Department of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden
Harvey M. Florman: Department of Obstetrics and Gynecology, University of Massachusetts Medical School Worcester, Worcester, MA, United States
U. Benjamin Kaupp: Center of Advanced European Studies and Research, Department of Molecular Sensory Systems, Bonn, Germany
U. Benjamin Kaupp: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
Timo Strünker: Center of Reproductive Medicine and Andrology, University Hospital Münster, University of Münster, Münster, Germany
Dagmar Wachten: Institute of Innate Immunity, Department of Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, Germany

DOI: https://doi.org/10.3389/fcell.2020.572735
Journal volume & issue: Vol. 8

Abstract

Read online

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 pHi 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 pHi 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.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

About the journal

Abstract

Keywords