Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
J Cell Biol. 2010 Jan 25;188(2):199-207. doi: 10.1083/jcb.200907161. Epub 2010 Jan 18.
After a long period of quiescence at dictyate prophase I, termed the germinal vesicle (GV) stage, mammalian oocytes reenter meiosis by activating the Cdc2-cyclin B complex (maturation-promoting factor [MPF]). The activity of MPF is regulated by Wee1/Myt1 kinases and Cdc25 phosphatases. In this study, we demonstrate that the sequestration of components that regulate MPF activity in distinct subcellular compartments is essential for their function during meiosis. Down-regulation of either Wee1B or Myt1 causes partial meiotic resumption, and oocytes reenter the cell cycle only when both proteins are down-regulated. Shortly before GV breakdown (GVBD), Cdc25B is translocated from the cytoplasm to the nucleus, whereas Wee1B is exported from the nucleus to the cytoplasm. These movements are regulated by PKA inactivation and MPF activation, respectively. Mislocalized Wee1B or Myt1 is not able to maintain meiotic arrest. Thus, cooperation of Wee1B, Myt1, and Cdc25 is required to maintain meiotic arrest and relocation of these components before GVBD is necessary for meiotic reentry.
在有丝分裂前期的 Dictyate 期经历了长时间的静止期后，称为生发泡期（GV），哺乳动物卵母细胞通过激活 Cdc2-细胞周期蛋白 B 复合物（成熟促进因子 [MPF]）重新进入减数分裂。MPF 的活性受 Wee1/Myt1 激酶和 Cdc25 磷酸酶调节。在这项研究中，我们证明了调节 MPF 活性的成分在不同的亚细胞隔室中的隔离对于它们在减数分裂中的功能是必不可少的。下调 Wee1B 或 Myt1 会导致部分减数分裂恢复，只有当两种蛋白质都下调时，卵母细胞才会重新进入细胞周期。在 GV 破裂（GVBD）之前不久，Cdc25B 从细胞质转移到细胞核，而 Wee1B 则从细胞核输出到细胞质。这些运动分别受 PKA 失活和 MPF 激活调节。定位错误的 Wee1B 或 Myt1 无法维持减数分裂阻滞。因此，Wee1B、Myt1 和 Cdc25 的合作对于维持减数分裂阻滞以及在 GVBD 之前这些成分的重新定位是必需的，这对于减数分裂的重新进入是必要的。
