Mediation of sperm-egg fusion:: evidence that mouse egg α6β1 integrin is the receptor for sperm fertilinβ

Introduction: A key step leading to fertilization is the binding of sperm to the egg plasma membrane. When a mammalian sperm reaches the egg plasma membrane, fertilin beta, an extracellular sperm "membrane protein, ig believed to bind to an egg plasma membrane receptor triggering fusion. We set out to identify the fertilin beta binding partner on the egg plasma membrane. Results: We synthesized an I-125-labeled peptide with the consensus Asp-Glu-Cys-Asp (DECD) sequence of fertilin beta's disintegrin domain. This peptide contains a benzophenone photoaffinity probe and inhibits sperm-egg fusion. Upon photoactivation in the presence of whole mouse eggs, a single polypeptide was covalently labeled. This polypeptide has been identified by immunoprecipitation as an alpha(6) integrin complexed with beta(1) integrin. Conclusions: Our experiments establish that small peptides containing the consensus DECD sequence of sperm fertilin beta bind specifically to an alpha(6)beta(1) integrin receptor on the egg membrane. We conclude that fertilin beta binds directly to the alpha(6)beta(1) integrin on the egg surface and this partnership mediates sperm-egg fusion.