Hou Chenxi, Yu Fazhi, Cao Cheng, Wang Tianchen, Pan Zihang, Zhong Mingru, Liu Xing, Yao Xuebiao, Zhang Kaiguang, Yang Zhenye, Guo Jing
Department of Digestive disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
MOE Key Laboratory for Cellular Dynamics, University of Science and Technology of China, Hefei 230027, China.
J Mol Cell Biol. 2025 Dec 29;17(5). doi: 10.1093/jmcb/mjaf023.
Cells round up when they enter mitosis and maintain this rounded morphology until they pass the spindle assembly checkpoint during anaphase. However, the mechanisms that regulate and maintain this transient spherical state remain unclear. In this study, we demonstrate that both astral microtubules and Aurora B kinase are required to maintain cortex stability during prometaphase. Simultaneous inhibition of astral microtubules and Aurora B leads to severe and continuous deformation of mitotic cells, resulting in micronuclei containing chromosomes after the cells exit mitosis. Mechanistically, active Aurora B kinase reduces the activity of myosin light chain kinase through phosphorylation, which in turn decreases the motor activity of myosin II. Additionally, Aurora B kinase regulates the distribution of actin at the cortex by phosphorylating the intermediate filament protein vimentin. Blocking these phosphorylation events disrupts the para-cortex localization of vimentin around the cortex and leads to the dislocalization of actin at the cortex. These regulatory effects occur in highly mobile cells expressing vimentin. In summary, we show that during mitosis, Aurora B kinase coordinates the interactions between microtubules, actin, and intermediate filaments to stabilize the cortex of rounded mitotic cells, ensuring the successful completion of mitosis.
细胞进入有丝分裂时会变圆,并保持这种圆形形态,直到它们在后期通过纺锤体组装检查点。然而,调节和维持这种短暂球形状态的机制仍不清楚。在本研究中,我们证明星状微管和极光B激酶在有丝分裂前期维持皮质稳定性方面都是必需的。同时抑制星状微管和极光B会导致有丝分裂细胞严重且持续变形,导致细胞退出有丝分裂后出现含有染色体的微核。从机制上讲,活跃的极光B激酶通过磷酸化降低肌球蛋白轻链激酶的活性,进而降低肌球蛋白II的运动活性。此外,极光B激酶通过磷酸化中间丝蛋白波形蛋白来调节肌动蛋白在皮质的分布。阻断这些磷酸化事件会破坏波形蛋白在皮质周围的副皮质定位,并导致肌动蛋白在皮质的错位。这些调节作用发生在表达波形蛋白的高迁移率细胞中。总之,我们表明在有丝分裂期间,极光B激酶协调微管、肌动蛋白和中间丝之间的相互作用,以稳定圆形有丝分裂细胞的皮质,确保有丝分裂的成功完成。