Sperm-derived WW domain-binding protein, PAWP, elicits calcium oscillations and oocyte activation in humans and mice
Sperm-derived WW domain-binding protein, PAWP, elicits calcium oscillations and oocyte activation in humans and mice
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DOI：
10.1096/fj.14-256495
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发表时间：
2014-10-01
期刊：
影响因子：
4.8
通讯作者：
Oko, Richard
中科院分区：
文献类型：
--
作者：
Aarabi, Mahmoud;Balakier, Hanna;Oko, Richard
哺乳动物受精卵的发育是由精子介导的细胞内钙振荡启动的，随后激活中期II受阻的卵母细胞。精子顶体后WW结合蛋白(PAWP)通过诱导卵母细胞激活并储存在核周膜(在受精过程中其内容物首先释放到卵母细胞细胞质中)来满足卵母细胞激活因子的标准。然而，PAWP启动哺乳动物受精卵发育的证据依赖于它作用于卵母细胞钙振荡的上游的证据。在这里，我们展示了PAWP在人类和小鼠卵母细胞中触发钙振荡和原核形成，类似于在卵胞浆内单精子注射(ICSI)中观察到的情况。最重要的是，通过共同注射来自PAWP的WWI结构域结合基序的竞争性抑制物，可以阻止精子诱导的钙振荡，这意味着精子PAWP和卵子来源的WWI结构域蛋白底物PAWP是成功受精所必需的。因此，精子传递的PAWP是一种独特的蛋白质，在人类和小鼠受精过程中具有非多余的作用，是触发合子发育所必需的。目前的数据证实了我们之前在非哺乳动物模型中的发现，并提出了PAWP在不孕不育诊断和治疗中的潜在应用。-Aarabi，M.，Balakier，H.，Bashar，S.，Moskovtsev，S.I.，Sutovsky，P.，Librach，C.L.和Oko，R.精子衍生的WW结构域结合蛋白PAWP在人类和小鼠中引起钙离子振荡和卵母细胞激活。
Mammalian zygotic development is initiated by sperm-mediated intracellular calcium oscillations, followed by activation of metaphase II-arrested oocytes. Sperm postacrosomal WW binding protein (PAWP) fulfils the criteria set for an oocyte-activating factor by inducing oocyte activation and being stored in the perinuclear theca, the sperm compartment whose content is first released into oocyte cytoplasm during fertilization. However, proof that PAWP initiates mammalian zygotic development relies on demonstration that it acts upstream of oocyte calcium oscillations. Here, we show that PAWP triggers calcium oscillations and pronuclear formation in human and mouse oocytes similar to what is observed during intracytoplasmic sperm injection (ICSI). Most important, sperm-induced calcium oscillations are blocked by coinjection of a competitive inhibitor, derived from the WWI domain-binding motif of PAWP, implying the requirement of sperm PAWP and an oocyte-derived WWI domain protein substrate of PAWP for successful fertilization. Sperm-delivered PAWP is, therefore, a unique protein with a nonredundant role during human and mouse fertilization, required to trigger zygotic development. Presented data confirm our previous findings in non-mammalian models and suggest potential applications of PAWP in the diagnosis and treatment of infertility.-Aarabi, M., Balakier, H., Bashar, S., Moskovtsev, S. I., Sutovsky, P., Librach, C. L., and Oko, R. Sperm-derived WW domain-binding protein, PAWP, elicits calcium oscil-lations and oocyte activation in humans and mice.