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Asian Journal of Andrology (2012) 14, 816–821; doi:10.1038/aja.2012.81; published online 24 September 2012
Mechanism of sperm capacitation and the acrosome reaction: role of protein kinases
Debby Ickowicz, Maya Finkelstein and Haim Breitbart
The Mina & Everard Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52100, Israel
Correspondence: Dr H Breitbart, (breith@mail.biu.ac.il)
Received 17 April 2012; Revised 30 May 2012; Accepted 8 July 2012
Advance online publication 24 September 2012
| Abstract |
Mammalian sperm must undergo a series of biochemical and physiological modifications, collectively called capacitation, in the female reproductive tract prior to the acrosome reaction (AR). The mechanisms of these modifications are not well characterized though protein kinases were shown to be involved in the regulation of intracellular Ca2+ during both capacitation and the AR. In the present review, we summarize some of the signaling events that are involved in capacitation. During the capacitation process, phosphatidyl-inositol-3-kinase (PI3K) is phosphorylated/activated via a protein kinase A (PKA)-dependent cascade, and downregulated by protein kinase C α (PKCα). PKCα is active at the beginning of capacitation, resulting in PI3K inactivation. During capacitation, PKCα as well as PP1γ2 is degraded by a PKA-dependent mechanism, allowing the activation of PI3K. The activation of PKA during capacitation depends mainly on cyclic adenosine monophosphate (cAMP) produced by the bicarbonate-dependent soluble adenylyl cyclase. This activation of PKA leads to an increase in actin polymerization, an essential process for the development of hyperactivated motility, which is necessary for successful fertilization. Actin polymerization is mediated by PIP2 in two ways: first, PIP2 acts as a cofactor for phospholipase D (PLD) activation, and second, as a molecule that binds and inhibits actin-severing proteins such as gelsolin. Tyrosine phosphorylation of gelsolin during capacitation by Src family kinase (SFK) is also important for its inactivation. Prior to the AR, gelsolin is released from PIP2 and undergoes dephosphorylation/activation, resulting in fast F-actin depolymerization, leading to the AR.
Keywords: sperm capacitation; acrosome reaction; AR; PKCα; PI3K; PKA; gelsolin; PIP2 |
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