Ion channels, phosphorylation and mammalian sperm capacitation

Abstract

Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies.

The Epididymis: Embryology, Structure, Function And Its Role In Fertilization And Infertility

“…Capacitation is a complex maturational phenomenon that renders spermatozoa capable of binding and fusing with the oocyte, which is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins (Visconti et al, 2011).…”

Odorant receptor-mediated sperm activation in disease vector mosquitoes

“…Asterisks indicate significant differences between compound and control buffer samples or between compound with or without VUANT (Mann-Whitney U, P < 0.01). The activation of insect sperm via ionotropic Ors is reminiscent of capacitation of mammalian sperm, which has been linked to signaling pathways mediated by metabotropic ORs (23,26,27) as well as the activity of several ionotropic channels (58,59). These include calcium channels, most notably the sperm cation channels, CatSpers (60)(61)(62)(63), potassium channels such as Kcnu1 (64,65) as well as sodium, proton, bicarbonate, and chloride channels that are localized along the sperm flagella and speculated to act downstream of receptors for diverse extracellular ligands (33,59).…”

Compartmentalization of Distinct cAMP Signaling Pathways in Mammalian Sperm

“…Effect of Forskolin on Phosphorylation Events Associated with Sperm Capacitation-Capacitation is associated with the activation of a cAMP/PKA-dependent signaling pathway leading to phosphorylation of Ser/Thr residues in PKA substrates followed by up-regulation of protein tyrosine phosphorylation (1,45). It was previously shown that cAMP synthesized by sAC could stimulate phosphorylation of a number of PKA substrate proteins, so we asked whether a FK-induced increase in cAMP could up-regulate similar phosphorylation events in sperm.…”

“…They acquire fertilizing capacity during their transit through the female tract in a process known as capacitation. This process includes the preparation for a physiologically induced acrosome reaction and for changes in the sperm motility pattern known as hyperactivation (1). Although the molecular basis of this process is not completely understood, it has been shown that different aspects of capacitation are regulated by the second messenger cAMP (reviewed in Refs.…”