Cdk1-mediated DIAPH1 phosphorylation maintains metaphase cortical tension and inactivates the spindle assembly checkpoint at anaphase
Cdk1-mediated DIAPH1 phosphorylation maintains metaphase cortical tension and inactivates the spindle assembly checkpoint at anaphase
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DOI：
10.1038/s41467-019-08957-w
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发表时间：
2019-02-28
影响因子：
16.6
通讯作者：
Nakanishi, Makoto
中科院分区：
文献类型：
--
作者：
Nishimura, Koutarou;Johmura, Yoshikazu;Nakanishi, Makoto
动物细胞在有丝分裂过程中经历快速的圆化，以确保适当的染色体分离，在此期间，向外圆整力在进入前中期时突然增加，并在中期保持恒定水平。最初的皮质张力是由肌球蛋白系统产生的，肌球蛋白马达和肌动蛋白网络结构都参与了这一系统。然而，皮质张力是如何维持的及其生理意义仍不清楚。我们在这里证明，CDK1介导的DIAPH1的磷酸化在舍入后稳定地维持皮质张力，并使纺锤体组装检查点(SAC)失活。CDK1使DIAPH1磷酸化，阻止profilin1结合以维持皮质张力。DIAPH1磷酸化位点的突变促进了皮质F-肌动蛋白的积累，增加了皮质张力，并推迟了由于SAC激活而导致的后期开始。对动粒内长度的测量表明，CDK1介导的皮质松弛是动粒伸展所必需的。因此，我们揭示了一个先前未知的机制，即CDK1在后期开始协调皮质张力维持和SAC失活。
Animal cells undergo rapid rounding during mitosis, ensuring proper chromosome segregation, during which an outward rounding force abruptly increases upon prometaphase entry and is maintained at a constant level during metaphase. Initial cortical tension is generated by the actomyosin system to which both myosin motors and actin network architecture contribute. However, how cortical tension is maintained and its physiological significance remain unknown. We demonstrate here that Cdk1-mediated phosphorylation of DIAPH1 stably maintains cortical tension after rounding and inactivates the spindle assembly checkpoint (SAC). Cdk1 phosphorylates DIAPH1, preventing profilin1 binding to maintain cortical tension. Mutation of DIAPH1 phosphorylation sites promotes cortical F-actin accumulation, increases cortical tension, and delays anaphase onset due to SAC activation. Measurement of the intrakinetochore length suggests that Cdk1-mediated cortex relaxation is indispensable for kinetochore stretching. We thus uncovered a previously unknown mechanism by which Cdk1 coordinates cortical tension maintenance and SAC inactivation at anaphase onset.