Kim Hyun-Jung, Lee Su-Yeon, Lee Hyun-Seo, Kim Eun-Young, Ko Jung-Jae, Lee Kyung-Ah
a Fertility Center of CHA Gangnam Medical Center , College of Medicine, CHA University , Seoul , Korea.
b Institute of Reproductive Medicine , Department of Biomedical Science, College of Life Science, CHA University , Pan-Gyo , Korea.
Cell Cycle. 2017 Aug 18;16(16):1534-1546. doi: 10.1080/15384101.2017.1339847. Epub 2017 Jul 26.
In previous studies, we observed that Zeta-chain-associated protein kinase 70 (Zap70) regulates spindle assembly and chromosome alignment in mouse oocyte and that Ran binding protein 2 (RanBP2) is a highly associated gene with Zap70 based on a microarray analysis. Because RanBP2 is related to nuclear envelope breakdown (NEBD) during mitosis, the aim of the present study was to elucidate the molecular mechanism of Zap70 with respect to RanBP2 in the germinal vesicle breakdown (GVBD) of oocytes. Results indicated that RanBP2 expression was regulated by Zap70 and that depletion of RanBP2 using RanBP2 RNAi manifested comparable phenotypes to those observed in Zap70 RNAi-treated oocytes, which presented faster processing of GVBD. Additionally, Zap70 RNAi-treated oocytes showed faster meiotic resumption with premature activation of maturation-promoting factor (MPF), premature division of chromosomes at approximately 6-8 h and more rapid degradation of securin. In conclusion, we report that Zap70 is a crucial factor for controlling the exact timing of meiotic progression in mouse oocytes.
在先前的研究中,我们观察到ζ链相关蛋白激酶70(Zap70)调节小鼠卵母细胞中的纺锤体组装和染色体排列,并且基于微阵列分析,Ran结合蛋白2(RanBP2)是与Zap70高度相关的基因。由于RanBP2与有丝分裂期间的核膜破裂(NEBD)相关,本研究的目的是阐明Zap70在卵母细胞生发泡破裂(GVBD)过程中与RanBP2相关的分子机制。结果表明,RanBP2的表达受Zap70调节,使用RanBP2 RNAi耗尽RanBP2表现出与在Zap70 RNAi处理的卵母细胞中观察到的类似表型,后者表现出更快的GVBD进程。此外,Zap70 RNAi处理的卵母细胞表现出更快的减数分裂恢复,伴有成熟促进因子(MPF)的过早激活、在大约6 - 8小时时染色体的过早分离以及securin的更快降解。总之,我们报道Zap70是控制小鼠卵母细胞减数分裂进程精确时间的关键因素。