Centre for Gene Regulation and Expression, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Ludwig Institute for Cancer Research, San Diego, United States.
Elife. 2020 Dec 23;9:e65307. doi: 10.7554/eLife.65307.
Protein Phosphatase 2A (PP2A) is a heterotrimer composed of scaffolding (A), catalytic (C), and regulatory (B) subunits. PP2A complexes with B56 subunits are targeted by Shugoshin and BUBR1 to protect centromeric cohesion and stabilise kinetochore-microtubule attachments in yeast and mouse meiosis. In , the closest BUBR1 orthologue lacks the B56-interaction domain and Shugoshin is not required for meiotic segregation. Therefore, the role of PP2A in female meiosis is unknown. We report that PP2A is essential for meiotic spindle assembly and chromosome dynamics during female meiosis. BUB-1 is the main chromosome-targeting factor for B56 subunits during prometaphase I. BUB-1 recruits PP2A:B56 to the chromosomes via a newly identified LxxIxE motif in a phosphorylation-dependent manner, and this recruitment is important for proper chromosome congression. Our results highlight a novel mechanism for B56 recruitment, essential for recruiting a pool of PP2A involved in chromosome congression during meiosis I.
蛋白磷酸酶 2A（PP2A）是一种由支架（A）、催化（C）和调节（B）亚基组成的异三聚体。与 B56 亚基结合的 PP2A 复合物被 Shugoshin 和 BUBR1 靶向，以保护着丝粒的黏合，并稳定酵母和小鼠减数分裂中的动粒微管附着。在 中，最接近的 BUBR1 同源物缺乏与 B56 相互作用的结构域，减数分裂分离不需要 Shugoshin。因此，PP2A 在 雌性减数分裂中的作用尚不清楚。我们报告说，PP2A 对于 雌性减数分裂中的纺锤体组装和染色体动力学是必需的。BUB-1 是前期 I 中 B56 亚基的主要染色体靶向因子。BUB-1 通过一个新发现的 LxxIxE 基序以磷酸化依赖性的方式将 PP2A:B56 募集到染色体上，这种募集对于正确的染色体向心性排列是重要的。我们的结果强调了 B56 募集的一种新机制，对于在减数分裂 I 中募集参与染色体向心性排列的 PP2A 池是必需的。
