Cohen G, Rubinstein S, Gur Y, Breitbart H
Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
Dev Biol. 2004 Mar 1;267(1):230-41. doi: 10.1016/j.ydbio.2003.10.034.
Mammalian spermatozoa should reside in the female reproductive tract for a certain time before gaining the ability to fertilize. During this time, the spermatozoa undergo a series of biochemical processes collectively called capacitation. We recently demonstrated that actin polymerization is a necessary step in the cascade leading to capacitation. We demonstrate here for the first time a role for phospholipase D (PLD) in the induction of actin polymerization and capacitation in spermatozoa. The involvement of PLD is supported by specific inhibition of F-actin formation during sperm capacitation by PLD inhibitors and the stimulation of fast F-actin formation by exogenous PLD or phosphatidic acid (PA). Moreover, PLD activity is enhanced during capacitation before actin polymerization. Protein kinase A (PKA), known to be active in sperm capacitation, and protein kinase C (PKC), involved in the acrosome reaction, can both activate PLD and actin polymerization. We suggest that PKA- and PKC-dependent signal transduction pathways can potentially lead to PLD activation; however, under physiological conditions, actin polymerization depends primarily on PKA activity. Activation of PKA during capacitation causes inactivation of phospholipase C, and as a result, PKC activation is prevented. It appears that PKA activation promotes sperm capacitation whereas early activation of PKC during capacitation would jeopardize this process.
哺乳动物的精子在获得受精能力之前，需要在雌性生殖道中停留一段时间。在此期间，精子会经历一系列统称为获能的生化过程。我们最近证明，肌动蛋白聚合是导致获能的级联反应中的一个必要步骤。我们在此首次证明磷脂酶D（PLD）在精子肌动蛋白聚合诱导和获能过程中的作用。PLD抑制剂在精子获能过程中对F-肌动蛋白形成的特异性抑制以及外源性PLD或磷脂酸（PA）对快速F-肌动蛋白形成的刺激，都支持了PLD的参与。此外，在肌动蛋白聚合之前的获能过程中，PLD活性增强。已知在精子获能中起作用的蛋白激酶A（PKA）和参与顶体反应的蛋白激酶C（PKC），都可以激活PLD和肌动蛋白聚合。我们认为，PKA和PKC依赖的信号转导途径可能会导致PLD激活；然而，在生理条件下，肌动蛋白聚合主要依赖于PKA活性。获能过程中PKA的激活会导致磷脂酶C失活，结果是阻止了PKC的激活。看来PKA激活促进精子获能，而获能过程中PKC过早激活会危及这一过程。
