Zhang Qing-Hua, Yuen Wai Shan, Adhikari Deepak, Flegg Jennifer A, FitzHarris Greg, Conti Marco, Sicinski Piotr, Nabti Ibtissem, Marangos Petros, Carroll John
Development and Stem Cell Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
J Cell Biol. 2017 Oct 2;216(10):3133-3143. doi: 10.1083/jcb.201607111. Epub 2017 Aug 17.
Cyclin A2 is a crucial mitotic Cdk regulatory partner that coordinates entry into mitosis and is then destroyed in prometaphase within minutes of nuclear envelope breakdown. The role of cyclin A2 in female meiosis and its dynamics during the transition from meiosis I (MI) to meiosis II (MII) remain unclear. We found that cyclin A2 decreases in prometaphase I but recovers after the first meiotic division and persists, uniquely for metaphase, in MII-arrested oocytes. Conditional deletion of cyclin A2 from mouse oocytes has no discernible effect on MI but leads to disrupted MII spindles and increased merotelic attachments. On stimulation of exit from MII, there is a dramatic increase in lagging chromosomes and an inhibition of cytokinesis. These defects are associated with an increase in microtubule stability in MII spindles, suggesting that cyclin A2 mediates the fidelity of MII by maintaining microtubule dynamics during the rapid formation of the MII spindle.
细胞周期蛋白A2是一种关键的有丝分裂周期蛋白依赖性激酶(Cdk)调节伴侣,它协调进入有丝分裂,然后在核膜破裂后的几分钟内,在前中期被降解。细胞周期蛋白A2在雌性减数分裂中的作用及其在从减数分裂I(MI)到减数分裂II(MII)过渡期间的动态变化仍不清楚。我们发现,细胞周期蛋白A2在前中期I减少,但在第一次减数分裂后恢复,并在MII期停滞的卵母细胞中独特地持续存在于中期。从小鼠卵母细胞中条件性缺失细胞周期蛋白A2对MI没有明显影响,但会导致MII纺锤体紊乱和着丝粒外附着增加。在刺激从MII期退出时,滞后染色体显著增加,细胞分裂受到抑制。这些缺陷与MII纺锤体中微管稳定性增加有关,表明细胞周期蛋白A2通过在MII纺锤体快速形成过程中维持微管动态来介导MII的保真度。