MODELING HUMAN SPERM-EGG INTERACTIONS IN-VITRO - SIGNAL-TRANSDUCTION PATHWAYS REGULATING THE ACROSOME REACTION

Recent advances in characterizing sperm surface receptors and ion chan nels, when combined with the rapidly expanding knowlege of interaction s among second messenger systems in somatic cells, permit formulation of a tentative molecular mechanism for the regulation of the human spe rm acrosome reaction. As spermatozoa pass through the cumulus mass, pr ogesterone binds to its sperm surface receptor, alkalinizes the sperm head cytosol and potentiates changes in intracellular ionized calcium. Primary binding of spermatozoa to egg involves receptors for mannosyl , N-acetyglucosaminyl and, possibly, fucosyl residues of the glycosyla ted zona protein, ZP3. These receptors aggregate on multivalent ligand binding, migrate to the equatorial region along an actin filament net work formed between the plasma and acrosomal membranes during capacita tion, and activate a G protein/protein kinase A/protein kinase C secon d messenger system and a secondary proteolysis signal. Binding of a re ceptor tyrosine kinase to ZP3 amino acid residues simultaneous with th e sugar recognition event triggers tyrosine phosphorylation signalling . All signals combine to open a voltage-dependent calcium channel. The resulting elevated calcium signal depolymerizes the inter-membrane ac tin network and activates phospholipases, leading to an acrosome react ion.