Cdk1 negatively regulates the spindle localization of Prc1 in mouse oocytes
Cdk1 negatively regulates the spindle localization of Prc1 in mouse oocytes
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DOI：
10.1111/gtc.12803
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发表时间：
2020-09-21
期刊：
影响因子：
2.1
通讯作者：
Kitajima, Tomoya S.
中科院分区：
文献类型：
--
作者：
Nishiyama, Sui;Yoshida, Shuhei;Kitajima, Tomoya S.
染色体分离需要形成双极纺锤体。小鼠卵母细胞减数分裂I期间无中心体纺锤体的及时双极化取决于反平行微管交联剂Prc 1。Prc1在卵母细胞中的调节方式仍然知之甚少。在这项研究中，我们表明，激酶Cdk1负调控纺锤体定位Prc1在小鼠卵母细胞。Cdk1活性的急性抑制导致Prc1在纺锤体和动粒的过度定位，而Cdk1的过度激活则具有相反的效果。在Cdk1介导的磷酸化位点上携带突变的Prc1的过表达增加了其在纺锤体上的定位，加速了纺锤体的双极化，并在中期I引起了纺锤体检查点依赖性的阻滞。Cdk1的过度激活延迟了纺锤体的双极化，而Prc1的磷酸化突变体形式的过度表达却不能逆转这一现象。这些结果表明，Cdk1介导的磷酸化负调控Prc1的本地化，以确保在哺乳动物卵母细胞减数分裂I的无中心体纺锤体的及时双极化。
Chromosome segregation requires the formation of a bipolar spindle. The timely bipolarization of the acentrosomal spindle during meiosis I in mouse oocytes depends on the antiparallel microtubule crosslinker Prc1. How Prc1 is regulated in oocytes remains poorly understood. In this study, we show that the kinase Cdk1 negatively regulates the spindle localization of Prc1 in mouse oocytes. The acute inhibition of Cdk1 activity led to excessive localization of Prc1 at the spindle and kinetochores, whereas the overactivation of Cdk1 had opposite effects. The overexpression of Prc1 carrying mutations at Cdk1-mediated phosphorylation sites increased its localization to the spindle, accelerated spindle bipolarization and caused spindle-checkpoint-dependent arrest at metaphase I. Overactivation of Cdk1 delayed spindle bipolarization, which was reversed by the overexpression of a phospho-mutant form but not the wild-type form of Prc1. These results suggest that Cdk1-mediated phosphorylation negatively regulates Prc1 localization to ensure the timely bipolarization of the acentrosomal spindle during meiosis I in mammalian oocytes.