Multiple requirements of PLK1 during mouse oocyte maturation.
Multiple requirements of PLK1 during mouse oocyte maturation.
复制标题
小鼠卵母细胞成熟过程中 PLK1 的多种需求。
DOI：
10.1371/journal.pone.0116783
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ellenberg J
中科院分区：
文献类型：
--
作者：
Solc P;Kitajima TS;Yoshida S;Brzakova A;Kaido M;Baran V;Mayer A;Samalova P;Motlik J;Ellenberg J
Polo样激酶1（PLK 1）协调细胞分裂的多个事件。虽然PLK 1的功能已被深入研究，在含有中心粒和快速循环的体细胞，少得多的是知道它在哺乳动物卵母细胞的减数分裂的功能，这在减数分裂恢复前的前期停滞了很长一段时间，缺乏纺锤体组装的中心粒。在这里，使用特定的小分子抑制结合活小鼠卵母细胞成像，我们全面表征减数分裂PLK 1的功能。我们发现，PLK 1在减数分裂恢复微管组织中心（MTOCs），后来在动粒被激活。PLK 1是通过促进核膜破裂而有效恢复减数分裂所必需的。PLK 1也需要募集中心体蛋白到无中心粒MTOC，以促进正常的纺锤体形成，以及稳定的着丝粒-微管附着。因此，PLK 1抑制导致中期I停滞，未对齐的染色体激活纺锤体组装检查点（SAC）。与有丝分裂不同的是，中期I停滞不会被SAC的失活所绕过。我们表明，PLK 1是所需的后期促进复合物/细胞周期体（APC/C）的完全激活，通过促进降解的APC/C抑制剂EMI 1，因此是必不可少的进入后期I。此外，我们的数据表明，PLK 1是所需的适当的染色体分离和维持染色体凝聚在减数分裂I-II过渡，独立的APC/C。因此，我们的研究结果定义了PLK 1在卵母细胞减数分裂中的作用，并揭示了哺乳动物有丝分裂和卵母细胞减数分裂对PLK 1的不同要求。
Polo-like kinase 1 (PLK1) orchestrates multiple events of cell division. Although PLK1 function has been intensively studied in centriole-containing and rapidly cycling somatic cells, much less is known about its function in the meiotic divisions of mammalian oocytes, which arrest for a long period of time in prophase before meiotic resumption and lack centrioles for spindle assembly. Here, using specific small molecule inhibition combined with live mouse oocyte imaging, we comprehensively characterize meiotic PLK1’s functions. We show that PLK1 becomes activated at meiotic resumption on microtubule organizing centers (MTOCs) and later at kinetochores. PLK1 is required for efficient meiotic resumption by promoting nuclear envelope breakdown. PLK1 is also needed to recruit centrosomal proteins to acentriolar MTOCs to promote normal spindle formation, as well as for stable kinetochore-microtubule attachment. Consequently, PLK1 inhibition leads to metaphase I arrest with misaligned chromosomes activating the spindle assembly checkpoint (SAC). Unlike in mitosis, the metaphase I arrest is not bypassed by the inactivation of the SAC. We show that PLK1 is required for the full activation of the anaphase promoting complex/cyclosome (APC/C) by promoting the degradation of the APC/C inhibitor EMI1 and is therefore essential for entry into anaphase I. Moreover, our data suggest that PLK1 is required for proper chromosome segregation and the maintenance of chromosome condensation during the meiosis I-II transition, independently of the APC/C. Thus, our results define the meiotic roles of PLK1 in oocytes and reveal interesting differential requirements of PLK1 between mitosis and oocyte meiosis in mammals.
登录
查看更多内容
DOI：
10.1038/nrm3494
发表时间：
2013-01
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1083/jcb.129.6.1617
发表时间：
1995-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Golsteyn RM;Mundt KE;Fry AM;Nigg EA
通讯作者：
Nigg EA
影响因子：
3.7
作者：
Brennan IM;Peters U;Kapoor TM;Straight AF
通讯作者：
Straight AF
DOI：
10.1073/pnas.0701140104
发表时间：
2007-03-13
影响因子：
11.1
作者：
Burkard, Mark E.;Randall, Catherine L.;Jallepalli, Prasad V.
通讯作者：
Jallepalli, Prasad V.
影响因子：
9.8
作者：
Hauf S;Roitinger E;Koch B;Dittrich CM;Mechtler K;Peters JM
通讯作者：
Peters JM