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, fertilinβ, an extracellular sperm membrane protein, is believed to bind to an egg plasma membrane receptor triggering fusion. We set out to identify the fertilinβ binding partner on the egg plasma membrane. Results: We synthesized an ¹²⁵I-labeled peptide with the consensus Asp-Glu-Cys-Asp (DECD) sequence of fertilinβ'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 α₆ integrin complexed with β₁ integrin. Conclusions: Our experiments establish that small peptides containing the consensus DECD sequence of sperm fertilinβ bind specifically to an α₆β₁ integrin receptor on the egg membrane. We conclude that fertilinβ binds directly to the α₆β₁ integrin on the egg surface and this partnership mediates sperm-egg fusion.