title: Sperm epidermal growth factor receptor (EGFR) mediates α7 acetylcholine receptor (AChR) activation to promote fertilization.
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.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Jaldety
authors.forename: Yair
authors.initials: Y
authors.lastname: Glick
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
authors.forename: Debby
authors.initials: D
authors.lastname: Ickowicz
authors.forename: Doron
authors.initials: D
authors.lastname: Gerber
authors.forename: Haim
authors.initials: H
authors.lastname: Breitbart
mesh_terms: D020101:Acrosome Reaction; D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005306:Fertilization; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046210:Microfluidic Analytical Techniques; D016133:Polymerase Chain Reaction / Q000379:methods; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism*; D015044:Zona Pellucida; D064569:alpha7 Nicotinic Acetylcholine Receptor; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D066246:ErbB Receptors; D019061:src-Family Kinases