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.

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at
You do not currently have access to this content.