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 mamma ls. Peptides corresponding to the disintegrin domain of fertilin and a ntibodies against fertilin have been shown to inhibit mammalian sperm- egg binding and fusion. A protein from the same family, xMDC16, was re cently cloned from frog (Xenopus laevis) testis and was found to be in volved in frog sperm-egg binding. Here we report that xMDC16 is locali zed predominantly on the posterior surface of egg jelly-activated sper m, and peptides from the disintegrin domain of this protein activate e ggs 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 p lasma membrane. This is the first demonstration of egg activation in v ertebrates by the surface application of a peptide derived from a sper m surface protein, supporting a model for egg activation that involves a signal transducing receptor for sperm in the egg's plasmamembrane. (C) 1998 Academic Press.