Voltage-Dependent Activation of Frog Eggs by a Sperm Surface Disintegrin Peptide

Fertilin, a sperm protein of the metalloprotease/disintegrin/cysteine-rich (MDC) family, plays a critical role in sperm–egg binding in mammals. Peptides corresponding to the disintegrin domain of fertilin and antibodies against fertilin have been shown to inhibit mammalian sperm–egg binding and fusion. A protein from the same family, xMDC16, was recently cloned from frog (Xenopus laevis) testis and was found to be involved in frog sperm–egg binding. Here we report that xMDC16 is localized predominantly on the posterior surface of egg jelly-activated sperm, and peptides from the disintegrin domain of this protein activate eggs when applied near the egg surface. Egg activation was dependent on (1) specific amino acid residues (KTX); (2) the presence of divalent cations, but not external Ca2+alone; and (3) voltage across the egg plasma membrane. This is the first demonstration of egg activation in vertebrates by the surface application of a peptide derived from a sperm surface protein, supporting a model for egg activation that involves a signal transducing receptor for sperm in the egg's plasma membrane.