Ca2+ signaling in mammalian spermatozoa.

Calcium is an essential ion which regulates sperm motility, capacitation and the acrosome reaction (AR), three processes necessary for successful fertilization. The AR enables the spermatozoon to penetrate into the egg. In order to undergo the AR, the spermatozoon must reside in the female reproductive tract for several hours, during which a series of biochemical transformations takes place, collectively called capacitation. An early event in capacitation is relatively small elevation of intracellular Ca2+ (in the nM range) and bicarbonate, which collectively activate the soluble adenylyl cyclase to produce cyclic-AMP; c-AMP activates protein kinase A (PKA), leading to indirect tyrosine phosphorylation of proteins. During capacitation, there is an increase in the membrane-bound phospholipase C (PLC) which is activated prior to the AR by relatively high increase in intracellular Ca2+ (in the μM range). PLC catalyzes the hydrolysis of phosphatidyl-inositol-4,5-bisphosphate (PIP2) to diacylglycerol and inositol-trisphosphate (IP3), leading to activation of protein kinase C (PKC) and the IP3-receptor. PKC activates a Ca2+- channel in the plasma membrane, and IP3 activates the Ca2+- channel in the outer acrosomal membrane, leading to Ca2+ depletion from the acrosome. As a result, the plasma-membrane store-operated Ca2+ channel (SOCC) is activated to increase cytosolic Ca2+ concentration, enabling completion of the acrosome reaction. The hydrolysis of PIP2 by PLC results in the release and activation of PIP2-bound gelsolin, leading to F-actin dispersion, an essential step prior to the AR. Ca2+ is also involved in the regulation of sperm motility. During capacitation, the sperm develops a unique motility pattern called hyper-activated motility (HAM) which is essential for successful fertilization. The main Ca2+-channel that mediates HAM is the sperm-specific CatSper located in the sperm tail.