Calmodulin signals capacitation and triggers the agonist-induced acrosome reaction in mouse spermatozoa

Capacitated acrosome-intact spermatozoa interact with specific sugar residu es on neoglycoproteins (ngps) or solubilized zona pellucida (ZP), the egg's extracellular glycocalyx, prior to the initiation of a signal transduction cascade that results in the fenestration and fusion of the sperm plasma me mbrane and the outer acrosomal membrane at multiple sites and exocytosis of acrosomal contents (i.e., induction of the acrosome reaction (AR)). The AR releases acrosomal contents at the site of spermzona binding and is though t to be a prerequisite event that allows spermatozoa to penetrate the ZP an d fertilize the egg. Since Ca2+/calmodulin (CaM) plays a significant role i n several cell signaling pathways and membrane fusion events, we have used a pharmacological approach to examine the role of CaM, a calcium-binding pr otein, in sperm capacitation and agonist-induced AR. Inclusion of CaM antag onists (calmodulin binding domain, calmidazolium, compound 48/80, ophioboli n A, W5, W7, and W13), either in in vitro capacitation medium or after sper m capacitation blocked the npg-/ZP-induced AR. Purified CaM largely reverse d the AR blocking effects of antagonists during capacitation. Our results d emonstrate that CaM plays an important role in priming (i.e., capacitation) of mouse spermatozoa as well as in the agonist-induced AR. These data allo w us to propose that CaM regulates these events by modulating sperm membran e component(s). (C) 2001 Academic Press.