Crosstalk between protein kinase A and C regulates phospholipase D and F-actin formation during sperm capacitation
Crosstalk between protein kinase A and C regulates phospholipase D and F-actin formation during sperm capacitation
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DOI：
10.1016/j.ydbio.2003.10.034
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发表时间：
2004-03-01
影响因子：
2.7
通讯作者：
Breitbart, H
中科院分区：
文献类型：
--
作者：
Cohen, G;Rubinstein, S;Breitbart, H
哺乳动物的精子在获得受精能力之前应该在雌性生殖道中停留一段时间。在此期间，精子经历一系列生物化学过程，统称为获能。我们最近证明，肌动蛋白聚合是一个必要的步骤级联导致获能。我们在这里首次证明了磷脂酶D（PLD）在精子肌动蛋白聚合和获能诱导中的作用。PLD的参与是由PLD抑制剂在精子获能过程中特异性抑制F-肌动蛋白形成和外源性PLD或磷脂酸（PA）刺激快速F-肌动蛋白形成所支持的。此外，PLD活性增强获能过程中肌动蛋白聚合之前。蛋白激酶A（PKA）和蛋白激酶C（PKC）参与精子获能，它们都能激活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，肌动蛋白聚合主要取决于PKA活性。获能过程中PKA的激活导致磷脂酶C的失活，结果，PKC的激活被阻止。PKA的激活促进精子获能，而在获能过程中PKC的早期激活会破坏这一过程。(C)2003年爱思唯尔公司All rights reserved.
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. (C) 2003 Elsevier Inc. All rights reserved.