Placenta-specific 1 regulates oocyte meiosis and fertilization through furin

Placenta-specific 1 regulates oocyte meiosis and fertilization through furin
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胎盘特异性 1 通过弗林蛋白酶调节卵母细胞减数分裂和受精

DOI:
10.1096/fj.201700922rr
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发表时间:
2018-10-01
期刊:
影响因子:
4.8
通讯作者:
Zhang, Dong
Zhang, Dong
中科院分区:
生物学2区
文献类型:
--
作者:
Shi, Li-Ya;Ma, Yang;Zhang, Dong

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胎盘特异性1 (placia -specific 1, Plac1)在胎盘形成中起着至关重要的作用,其异常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作用尚未阐明。在这里,我们报道了Plac1在小鼠卵母细胞中更为突出,并且在减数分裂过程中在膜区富集。一方面,Plac1敲低严重破坏了微绒毛组织;然而,另一方面,Plac1显著降低卵母细胞成熟,增加非整倍体,从而破坏正常受精。在免疫沉淀基质辅助激光解吸/电离的基础上,我们建立了一个工作模型,验证并提示,在生发囊泡阶段,Plac1富集膜激活furin,激活furin随后激活IGF-1受体,维持微绒毛的正常组织。在减数分裂开始时,活性的furin/IGF-1受体重新定位到细胞质中激活(磷酸化)Akt以促进减数分裂。综上所述,我们的发现表明,Plac1,一种对胎盘至关重要的蛋白,对卵母细胞减数分裂和受精也是必不可少的。施,L.-Y。,马,Y,朱,g -Y。刘俊伟;周,C.-X。陈立杰。王勇,李荣成。, Yang, Z.-X。胎盘特异性1通过furin调控卵母细胞减数分裂和受精。
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.