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Protein Regulator of Cytokinesis 1 (PRC1) Regulates Chromosome Dynamics and Cytoplasmic Division During Mouse Oocyte Meiotic Maturation and Early Embryonic Development.
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-06-19 , DOI: 10.1111/febs.15458
Cheng-Jie Zhou 1 , Dong-Hui Wang 1, 2 , Xiang-Wei Kong 1 , Zhe Han 1 , Xin Hao 1 , Xing-Yue Wang 1 , Xin Wen 1 , Cheng-Guang Liang 1
Affiliation  

In contrast to the homeokinesis of mitosis, asymmetric division of cytoplasm is the conspicuous feature of meiosis in mammalian oocytes. Protein regulator of cytokinesis 1 (PRC1) is an important regulator during mitotic spindle assembly and cytoplasmic division, but its functions in oocyte meiosis and early embryo development have not been fully elucidated. In this study, we detected PRC1 expression and localization and revealed a nuclear, spindle midzone‐related dynamic pattern throughout meiotic and mitotic progressions. Treatment of oocytes with the reagents taxol or nocodazole disturbed the distribution of PRC1 in metaphase II oocytes. Further, PRC1 depletion led to failure of first polar body (PB1) extrusion and spindle migration, aneuploidy and defective kinetochore–microtubule attachment and spindle assembly. Overexpression of PRC1 resulted in PB1 extrusion failure, aneuploidy and serious defects of spindle assembly. To investigate PRC1 function in early embryos, we injected Prc1 morpholino into zygotes and 2‐cell stage embryos. Depletion of PRC1 in zygotes impaired 4‐cell, morula and blastocyst formation. Loss of PRC1 in single or double blastomeres in 2‐cell stage embryos significantly impaired cell division, indicating its indispensable role in early embryo development. Co‐immunoprecipitation showed that PRC1 interacts with polo‐like kinase 1 (PLK1), and functional knockdown and rescue experiments demonstrated that PRC1 recruits PLK1 to the spindle midzone to regulate cytoplasmic division during meiosis. Finally, kinesin family member 4 knockdown downregulates PRC1 expression and leads to PRC1 localization failure. Taken together, our data suggest PRC1 plays an important role during oocyte maturation and early embryonic development by regulating chromosome dynamics and cytoplasmic division.

中文翻译:

胞质分裂1(PRC1)的蛋白质调节剂在小鼠卵母细胞减数分裂成熟和早期胚胎发育过程中调节染色体动力学和细胞质分裂。

与有丝分裂的同源性相反,细胞质的不对称分裂是哺乳动物卵母细胞减数分裂的明显特征。细胞分裂素1(PRC1)的蛋白质调节剂是有丝分裂纺锤体组装和细胞质分裂过程中的重要调节剂,但其在卵母细胞减数分裂和早期胚胎发育中的功能尚未得到充分阐明。在这项研究中,我们检测了PRC1的表达和定位,并揭示了整个减数分裂和有丝分裂进程中核,纺锤体中区相关的动态模式。用紫杉醇或诺考达唑试剂处理卵母细胞会干扰PRC1在中期II卵母细胞中的分布。此外,PRC1的耗尽导致第一极体(PB1)挤出和纺锤体迁移,非整倍性以及动粒-微管附着和纺锤体组装缺陷。PRC1的过表达导致PB1挤出失败,非整倍性和主轴组件的严重缺陷。为了研究PRC1在早期胚胎中的功能,我们注射了将Prc1吗啉代转化为受精卵和2细胞期胚胎。受精卵中PRC1的消耗会削弱4细胞,桑和囊胚的形成。2细胞阶段胚胎中单卵裂球或双卵裂球中PRC1的丧失会严重损害细胞分裂,表明其在早期胚胎发育中不可或缺的作用。免疫共沉淀表明PRC1与polo样激酶1(PLK1)相互作用,功能性敲低和抢救实验表明PRC1在减数分裂过程中将PLK1募集到纺锤体中部以调节细胞质分裂。最后,驱动蛋白家族成员4敲低下调PRC1的表达,并导致PRC1本地化失败。综上所述,我们的数据表明PRC1在卵母细胞成熟和早期胚胎发育中通过调节染色体动力学和细胞质分裂发挥重要作用。
更新日期:2020-06-19
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