The Christopher Chen Oocyte Biology Research Laboratory, Centre for Clinical Research, The University of Queensland, Herston, 4029 QLD, Australia.
The Christopher Chen Oocyte Biology Research Laboratory, Centre for Clinical Research, The University of Queensland, Herston, 4029 QLD, Australia.
Cell Rep. 2022 May 3;39(5):110789. doi: 10.1016/j.celrep.2022.110789.
Inactivation of cyclin-dependent kinase 1 (Cdk1), controlled by cyclin B1 proteolysis, orders events during mitotic exit. Here, we used a FRET biosensor to study Cdk1 activity while simultaneously monitoring anaphase II and pronuclear (PN) formation in live mouse eggs throughout fertilization. We find that Cdk1 inactivation occurs over two phases separated by a 3-h pause, the first induces anaphase II and the second induces PN formation. Although both phases require the inhibitory Cdk1 kinase Wee1B, only the first involves cyclin B1 proteolysis. Enforcing the 3-h pause is critical for providing the delay required for male PN formation and is mediated by spindle midzone-dependent sequestration of Wee1B between the first and second phases. Thus, unlike continuous Cdk1 inactivation driven by cyclin B1 proteolysis during mitotic exit, MII oocytes engineer a physiologically important pause during fertilization involving two different pathways to inactivate Cdk1, only the first of which requires proteolysis.
细胞周期蛋白依赖性激酶 1（Cdk1）的失活受细胞周期蛋白 B1 蛋白水解的控制，为有丝分裂后期的事件排序。在这里，我们使用 FRET 生物传感器在活的小鼠卵受精过程中同时监测有丝分裂后期 II 和原核（PN）形成来研究 Cdk1 的活性。我们发现 Cdk1 的失活分为两个阶段，中间有 3 小时的暂停，第一阶段诱导有丝分裂后期 II，第二阶段诱导 PN 形成。虽然这两个阶段都需要抑制性 Cdk1 激酶 Wee1B，但只有第一阶段涉及细胞周期蛋白 B1 蛋白水解。强制暂停 3 小时对于提供形成雄性 PN 所需的延迟至关重要，这是通过纺锤体中间区在第一和第二阶段之间将 Wee1B 隔离来介导的。因此，与有丝分裂后期细胞周期蛋白 B1 蛋白水解驱动的连续 Cdk1 失活不同，MII 卵在受精过程中设计了一个涉及两种不同途径的生理重要的暂停来失活 Cdk1，只有第一途径需要蛋白水解。
