At mitotic entry, reorganization of the actomyosin cortex prompts cells to round-up. Proteins of the ezrin, radixin, and moesin family (ERM) play essential roles in this process by linking actomyosin forces to the plasma membrane. Yet, the cell-cycle signal that activates ERMs at mitotic entry is unknown. By screening a compound library using newly developed biosensors, we discovered that drugs that disassemble microtubules promote ERM activation. We further demonstrated that disassembly of interphase microtubules at mitotic entry directs ERM activation and metaphase cell rounding through GEF-H1, a Rho-GEF inhibited by microtubule binding, RhoA, and its kinase effector SLK. We finally demonstrated that GEF-H1 and Ect2, another Rho-GEF previously identified to control actomyosin forces, act together to drive activation of ERMs and cell rounding in metaphase. In summary, we report microtubule disassembly as a cell-cycle signal that controls a signaling network ensuring that actomyosin forces are efficiently integrated at the plasma membrane to promote cell rounding at mitotic entry.

中文翻译：

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间期微管拆卸是一种信号线索，可驱动有丝分裂进入时的细胞变圆

在有丝分裂进入时，肌动球蛋白皮质的重组促使细胞聚集。埃兹蛋白、根蛋白和模蛋白家族 (ERM) 的蛋白质通过将肌动球蛋白力与质膜连接起来，在此过程中发挥重要作用。然而，在有丝分裂进入时激活 ERM 的细胞周期信号尚不清楚。通过使用新开发的生物传感器筛选化合物库，我们发现分解微管的药物可促进 ERM 激活。我们进一步证明，有丝分裂入口处的间期微管解体通过 GEF-H1（一种受微管结合 RhoA 及其激酶效应子 SLK 抑制的 Rho-GEF）指导 ERM 激活和中期细胞变圆。我们最终证明，GEF-H1 和 Ect2（之前确定的另一种控制肌动球蛋白力的 Rho-GEF）共同作用，驱动 ERM 的激活和中期细胞变圆。总之，我们将微管分解报告为细胞周期信号，控制信号网络，确保肌动球蛋白力有效整合在质膜上，以促进有丝分裂进入时的细胞圆形化。