Modelling human sperm-egg interactions in vitro: signal transduction pathways regulating the acrosome reaction.
Recent advances in characterizing sperm surface receptors and ion channels, when combined with the rapidly expanding knowledge of interactions among second messenger systems in somatic cells, permit formulation of a tentative molecular mechanism for the regulation of the human sperm acrosome reaction. As spermatozoa pass through the cumulus mass, progesterone 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-acetylglucosaminyl and, possibly, fucosyl residues of the glycosylated zona protein, ZP3. These receptors aggregate on multivalent ligand binding, migrate to the equatorial region along an actin filament network formed between the plasma and acrosomal membranes during capacitation, and activate a G protein/protein kinase A/protein kinase C second messenger system and a secondary proteolysis signal. Binding of a receptor tyrosine kinase to ZP3 amino acid residues simultaneous with the 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 actin network and activates phospholipases, leading to an acrosome reaction.
Department of Obstetrics and Gynecology, North Shore University Hospital-New York University Medical College, Manhasset 11030, USA.
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D000177:Acrosome / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism; D006224:Cricetinae; D004527:Egg Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D017136:Ion Transport; D037181:Lectins, C-Type; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009030:Mosaicism; D010740:Phospholipases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013084:Sperm-Ovum Interactions; D000072216:Zona Pellucida Glycoproteins; D000076202:c-Mer Tyrosine Kinase
D015220:Calcium Channels; D004527:Egg Proteins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse; D011494:Protein Kinases; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D010740:Phospholipases; D002118:Calcium