Sperm epidermal growth factor receptor (EGFR) mediates α7 acetylcholine receptor (AChR) activation to promote fertilization.

The Journal of Biological Chemistry
Yael JaldetyHaim Breitbart

Abstract

To attain fertilization the spermatozoon binds to the egg zona pellucida (ZP) via sperm receptor(s) and undergoes an acrosome reaction (AR). Several sperm receptors have been described in the literature; however, the identity of this receptor is not yet certain. In this study, we suggest that the α7 nicotinic acetylcholine receptor (α7nAChR) might be a sperm receptor activated by ZP to induce epidermal growth factor receptor (EGFR)-mediated AR. We found that isolated ZP or α7 agonists induced the AR in sperm from WT but not α7-null spermatozoa, and the induced AR was inhibited by α7 or EGFR antagonists. Moreover, α7-null sperm showed very little binding to the egg, and microfluidic affinity in vitro assay clearly showed that α7nAChR, as well as EGFR, interacted with ZP3. Induction of EGFR activation and the AR by an α7 agonist was inhibited by a Src family kinase (SFK) inhibitor. In conclusion we suggest that activation of α7 by ZP leads to SFK-dependent EGFR activation, Ca(2+) influx, and the acrosome reaction.

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Citations

Sep 25, 2012·Asian Journal of Andrology·Debby IckowiczHaim Breitbart
Dec 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·Natalia AndersenCecilia Bouzat
Feb 12, 2014·Reproduction : the Official Journal of the Society for the Study of Fertility·E A A SantosA R Silva
Jul 16, 2014·Zygote : the Biology of Gametes and Early Embryos·Yael Jaldety, Haim Breitbart
Jul 19, 2015·BMC Systems Biology·Soudabeh Sabetian, Mohd Shahir Shamsir
May 15, 2015·Asian Journal of Andrology·Haim Breitbart, Maya Finkelstein
Mar 25, 2017·Biology of Reproduction·Alfredo Ramírez-RevecoIlona I Concha
Apr 15, 2014·Photochemistry and Photobiology·Shiran ShaharHaim Breitbart
Aug 8, 2020·Biology of Reproduction·Gagandeep Kaur Gahlay, Neha Rajput
Jul 18, 2019·Nature Communications·Chun-Yu LinJinn-Moon Yang
Jul 28, 2020·Molecular and Cellular Endocrinology·Maya FinkelsteinHaim Breitbart

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