Cdk1-dependent mitotic enrichment of cortical myosin II promotes cell rounding against confinement

Cdk1-dependent mitotic enrichment of cortical myosin II promotes cell rounding against confinement
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DOI:
10.1038/ncb3098
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发表时间:
2015-02-01
影响因子:
21.3
通讯作者:
Muller, Daniel J.
Muller, Daniel J.
中科院分区:
生物学1区
文献类型:
--
作者:
Ramanathan, Subramanian P.;Helenius, Jonne;Muller, Daniel J.

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肌动球蛋白依赖的有丝分裂变圆发生在细胞培养和组织中,在那里它参与细胞定位和上皮组织。肌动球蛋白是如何调节有丝分裂变圆的还不清楚。在这里,我们的特点是力学的单个有丝分裂细胞,而成像肌动球蛋白招聘到细胞皮质。在有丝分裂开始时,一个统一的DIAPH 1依赖的F-肌动蛋白皮质的组装与初始圆形相一致。此后,皮质富集的F-肌动蛋白保持稳定,而肌球蛋白II逐渐积累在皮质,和量的肌球蛋白在皮质与细胞内的压力。而F-肌动蛋白只提供短期(< 10秒)的机械变形阻力,肌球蛋白维持细胞内的压力持续时间较长(> 60秒)。我们的数据表明,肌球蛋白II的有丝分裂细胞皮质的渐进积累可能需要Cdk 1激活的p21激活的激酶,抑制肌球蛋白的招聘,和Rho激酶,刺激肌球蛋白招聘到皮质。
Actomyosin-dependent mitotic rounding occurs in both cell culture and tissue, where it is involved in cell positioning and epithelial organization. How actomyosin is regulated to mediate mitotic rounding is not well understood. Here we characterize the mechanics of single mitotic cells while imaging actomyosin recruitment to the cell cortex. At mitotic onset, the assembly of a uniform DIAPH1-dependent F-actin cortex coincides with initial rounding. Thereafter, cortical enrichment of F-actin remains stable while myosin II progressively accumulates at the cortex, and the amount of myosin at the cortex correlates with intracellular pressure. Whereas F-actin provides only short-term (< 10 s) resistance to mechanical deformation, myosin sustains intracellular pressure for a longer duration (> 60 s). Our data suggest that progressive accumulation of myosin II to the mitotic cell cortex probably requires the Cdk1 activation of both p21-activated kinases, which inhibit myosin recruitment, and of Rho kinase, which stimulates myosin recruitment to the cortex.