Analysis of Fertilin α (ADAM1)-mediated Sperm-Egg Cell Adhesion during Fertilization and Identification of an Adhesion-mediating Sequence in the Disintegrin-like Domain

Abstract

Fertilin α (also known as ADAM1) is a member of the ADAM (A disintegrin and A metalloprotease domain) family of proteins. In this study, we examine the mechanism of mouse fertilin α's in adhesion of sperm to the egg plasma membrane during fertilization. We find that recombinant forms of fertilin α corresponding to either the disintegrin-like domain or the cysteine-rich domain and the EGF-like repeat can perturb sperm-egg binding, suggesting that both of these domains can participate in fertilin α-mediated adhesion events. In further examination of the fertilin α disintegrin-like domain, we find that a subdomain of disintegrin-like domain with the sequence DLEECDCG outside the putative disintegrin loop but with homology to the fertilin β disintegrin loop can inhibit the binding of both sperm and recombinant fertilin α to eggs, suggesting that this is an adhesion-mediating motif of the fertilin α disintegrin-like domain. This sequence also inhibits the binding of recombinant fertilin β to eggs and thus is the first peptide sequence found to block two different sperm ligands. Finally, a monoclonal antibody to the tetraspanin protein CD9, KMC.8, inhibited the binding of recombinant fertilin α to eggs in one type of binding assay, suggesting that, under certain conditions, fertilin α may interact with a KMC.8-sensitive binding site on the egg plasma membrane.