ZP3 is Required for Germinal Vesicle Breakdown in Mouse Oocyte Meiosis.
ZP3 is Required for Germinal Vesicle Breakdown in Mouse Oocyte Meiosis.
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ZP3 是小鼠卵母细胞减数分裂中生殖囊泡分解所必需的
DOI：
10.1038/srep41272
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发表时间：
2017-02-01
影响因子：
4.6
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Gao LL;Zhou CX;Zhang XL;Liu P;Jin Z;Zhu GY;Ma Y;Li J;Yang ZX;Zhang D
ZP3是哺乳动物卵母细胞透明带(ZP)的主要成分，是正常生育所必需的，ZP3基因敲除会导致完全不育。ZP3通过识别精子结合和激活顶体反应来促进受精；然而，ZP3在哺乳动物卵母细胞中的其他细胞作用尚未报道。在本研究中，我们发现ZP3在早期在细胞核中有强烈的表达，并逐渐向ZP移位。通过特定的siRNA敲除ZP3显著抑制生发泡破裂(GVBD)(标志着减数分裂的开始)，显著降低MII卵母细胞的比例。为了研究ZP3介导的GVBD的调控机制，我们通过免疫沉淀和质谱仪鉴定了潜在的ZP3相互作用蛋白。我们确定蛋白酪氨酸磷酸酶、受体K型(Ptprk)、芳烃受体相互作用蛋白样蛋白1(Aipl1)和透明相关蛋白2(Diph2)是潜在的候选基因，并建立了一个工作模型来解释ZP3如何影响GVBD。最后，我们提供了ZP3调节Akt的磷酸化、层蛋白与核膜的结合以及肌动蛋白细胞骨架的组织的初步证据。这些发现有助于我们理解ZP3在GVBD中扮演的新角色。
ZP3 is a principal component of the zona pellucida (ZP) of mammalian oocytes and is essential for normal fertility, and knockout of ZP3 causes complete infertility. ZP3 promotes fertilization by recognizing sperm binding and activating the acrosome reaction; however, additional cellular roles for ZP3 in mammalian oocytes have not been yet reported. In the current study, we found that ZP3 was strongly expressed in the nucleus during prophase and gradually translocated to the ZP. Knockdown of ZP3 by a specific siRNA dramatically inhibited germinal vesicle breakdown (GVBD) (marking the beginning of meiosis), significantly reducing the percentage of MII oocytes. To investigate the ZP3-mediated mechanisms governing GVBD, we identified potential ZP3-interacting proteins by immunoprecipitation and mass spectrometry. We identified Protein tyrosine phosphatase, receptor type K (Ptprk), Aryl hydrocarbon receptor-interacting protein-like 1 (Aipl1), and Diaphanous related formin 2 (Diaph2) as potential candidates, and established a working model to explain how ZP3 affects GVBD. Finally, we provided preliminary evidence that ZP3 regulates Akt phosphorylation, lamin binding to the nuclear membraneviaAipl1, and organization of the actin cytoskeletonviaDiaph2. These findings contribute to our understanding of a novel role played by ZP3 in GVBD.