Department of Biological Sciences, Purdue University, West Lafayette, IN United States.
Department of Human Genetics, University of Michigan, Ann Arbor, MI United States.
Cell Cycle. 2023 Jul;22(13):1614-1636. doi: 10.1080/15384101.2023.2225924. Epub 2023 Jun 20.
Tightly controlled fluctuations in kinase and phosphatase activity play important roles in regulating M-phase transitions. Protein Phosphatase 1 (PP1) is one of these phosphatases, with oscillations in PP1 activity driving mitotic M-phase. Evidence from a variety of experimental systems also points to roles in meiosis. Here, we report that PP1 is important for M-phase transitions through mouse oocyte meiosis. We employed a unique small-molecule approach to inhibit or activate PP1 at distinct phases of mouse oocyte meiosis. These studies show that temporal control of PP1 activity is essential for the G2/M transition, metaphase I/anaphase I transition, and the formation of a normal metaphase II oocyte. Our data also reveal that inappropriate activation of PP1 is more deleterious at the G2/M transition than at prometaphase I-to-metaphase I, and that an active pool of PP1 during prometaphase is vital for metaphase I/anaphase I transition and metaphase II chromosome alignment. Taken together, these results establish that loss of oscillations in PP1 activity causes a range of severe meiotic defects, pointing to essential roles for PP1 in female fertility, and more broadly, M-phase regulation.
激酶和磷酸酶活性的严格控制波动在调节 M 期转变中起着重要作用。蛋白磷酸酶 1（PP1）就是其中一种磷酸酶，其活性的波动驱动有丝分裂 M 期。来自各种实验系统的证据也表明其在减数分裂中具有作用。在这里，我们报告 PP1 在通过小鼠卵母细胞减数分裂的 M 期转变中是重要的。我们采用了一种独特的小分子方法，在小鼠卵母细胞减数分裂的不同阶段抑制或激活 PP1。这些研究表明，PP1 活性的时间控制对于 G2/M 转换、中期 I/后期 I 转换以及正常中期 II 卵母细胞的形成是必不可少的。我们的数据还表明，在 G2/M 转换时，PP1 的不适当激活比在前期 I 到中期 I 时更具危害性，并且在前期中活跃的 PP1 池对于中期 I/后期 I 转换和中期 II 染色体排列是至关重要的。总之，这些结果表明 PP1 活性的波动丧失会导致一系列严重的减数分裂缺陷，这表明 PP1 在女性生育能力以及更广泛的 M 期调节中具有重要作用。
