Analysis of fertilin alpha (ADAM1)-mediated sperm-egg cell adhesion duringfertilization and identification of an adhesion-mediating sequence in the disintegrin-like domain

Fertilin alpha (also known as ADAM1) is a member of the ADAM ((A) under bar (d) under bar isintegrin and (A) under bar (m) under bar etalloprotease do main) family of proteins. In this study, we examine the mechanism of mouse fertilin alpha 's in adhesion of sperm to the egg plasma membrane during fe rtilization. We find that recombinant forms of fertilin alpha 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 thes e domains can participate in fertilin alpha -mediated adhesion events. In f urther examination of the fertilin alpha disintegrin-like domain, we find t hat a subdomain of disintegrin-like domain with the sequence DLEECDCG outsi de the putative disintegrin loop but with homology to the fertilin beta dis integrin loop can inhibit the binding of both sperm and recombinant fertili n a to eggs, suggesting that this is an adhesion-mediating motif of the fer tilin a disintegrin-like domain. This sequence also inhibits the binding of recombinant fertilin p to eggs and thus is the first peptide sequence foun d to block two different sperm ligands, Finally, a monoclonal antibody to t he tetraspanin protein CD9, KMC.8, inhibited the binding of recombinant fer tilin a to eggs in one type of binding assay, suggesting that, under certai n conditions, fertilin a may interact with a KMC.8-sensitive binding site o n the egg plasma membrane.