The research project proposed is directed towards an understanding of the molecular details of fertilization, focusing specifically on the interaction between the egg zona pellucida (ZP) and sperm, leading to sperm activation. Sperm activation (i.e. ZP-induction of acrosomal exocytosis) is analogous to ligand-receptor mediated signal transduction processes found in many somatic, secretory cells. Such signal transduction events are mediated by guanine nucleotide binding regulatory proteins (G proteins) associated with cell surface receptors. We have recently developed a cell- free sperm membrane preparation demonstrating ZP-induced G protein activation. This preparation can be solubilized, retaining signal transduction activity. These preparations will be used to examine the dynamics of ZP interaction with the sperm membrane as well as to identify the G protein(s) and coupled receptor(s) which mediate ZP-induced acrosomal exocytosis. These experiments will help elucidate signal transduction mechanisms controlling ZP activation of sperm. An increased understanding of the molecular nature of ZP-sperm interaction may lead to further treatment infertility problems and to the development of contraceptive therapies based on intervention prior to fertilization.
