Sperm capacitation is regulated by the crosstalk between protein kinase A and C.

The binding of capacitated sperm to the egg's zona pellucida stimulates it to undergo the acrosome reaction, a process which enables the sperm to penetrate the egg. Mammalian sperm capacitation and the acrosome reaction require remodeling of actin filaments. An increase in phospholipase D (PLD)-dependent actin polymerization occurs during capacitation whereas the increase in sperm intracellular calcium after its binding to the egg causes very fast actin depolymerization prior to the acrosome reaction. Protein kinase A (PKA) and C (PKC) can both activate sperm PLD and actin polymerization under in vitro incubation, however under physiological conditions, actin polymerization depends primarily on PKA activity. We suggest that PKA indirectly activates phosphatidylinositol 4-kinase to produce phosphatidylinositol 4,5-bisphosphate which is a cofactor for PLD activation. In addition, activation of PKA during capacitation inactivates phospholipase C resulting in preventing PKC activation. It appears that PKA activation promotes sperm capacitation whereas too early activation of PKC during capacitation would jeopardize this process. Thus, a refined balance between the two pathways is required for optimal and sustained activation during sperm capacitation.