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胎盘特异性蛋白 1 通过弗林蛋白酶调控卵母细胞减数分裂和受精。

Placenta-specific 1 regulates oocyte meiosis and fertilization through furin.

机构信息

State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

Department of Gynecology, Zhejiang Provincial People's Hospital, Hangzhou, China.

出版信息

FASEB J. 2018 Oct;32(10):5483-5494. doi: 10.1096/fj.201700922RR. Epub 2018 May 3.

Abstract

Placenta-specific 1 (Plac1) has been found to be essential for placentation, and abnormal Plac1 expression and distribution is highly correlated with preeclampsia and implantation failure; however, its function in mammalian oocytes has not been elucidated. Here, we report that Plac1 was more prominent in mouse oocytes and enriched at the membrane region throughout meiosis. On the one hand, Plac1 knockdown severely disrupted microvillus organization; however, on the other hand, Plac1 significantly decreased oocyte maturation and increased aneuploidy, consequently disrupting normal fertilization. On the basis of immunoprecipitate matrix-assisted laser desorption/ionization, we established a working model, then verified and suggested that, at the germinal vesicle stage, Plac1 enriches the membrane to activate furin, and active furin subsequently activates IGF-1 receptor to maintain regular microvillus organization. Upon meiosis onset, active furin/IGF-1 receptor relocates into the cytoplasm to activate (phosphorylate) Akt to promote meiosis. In summary, our finding suggests that Plac1, a protein that is crucial for placentation, is also essential for oocyte meiosis and fertilization.-Shi, L.-Y., Ma, Y., Zhu, G.-Y., Liu, J.-W., Zhou, C.-X., Chen, L.-J., Wang, Y., Li, R.-C., Yang, Z.-X., Zhang, D. Placenta-specific 1 regulates oocyte meiosis and fertilization through furin.

摘要

胎盘特异性蛋白 1(Plac1)对于胎盘形成至关重要,异常的 Plac1 表达和分布与子痫前期和着床失败高度相关;然而,其在哺乳动物卵母细胞中的功能尚未阐明。在这里,我们报告 Plac1 在小鼠卵母细胞中更为突出,并在整个减数分裂过程中富集在膜区域。一方面,Plac1 敲低严重破坏微绒毛组织;然而,另一方面,Plac1 显著降低卵母细胞成熟并增加非整倍体,从而破坏正常受精。基于免疫沉淀基质辅助激光解吸电离,我们建立了一个工作模型,然后验证并提出,在生发泡阶段,Plac1 富集在膜上以激活弗林蛋白酶,而活性弗林蛋白酶随后激活 IGF-1 受体以维持正常的微绒毛组织。减数分裂开始时,活性弗林蛋白酶/IGF-1 受体迁移到细胞质中,激活(磷酸化)Akt 以促进减数分裂。总之,我们的发现表明,对于胎盘形成至关重要的蛋白质 Plac1 对于卵母细胞减数分裂和受精也是必不可少的。

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