RhoA is required for cortical retraction and rigidity during mitotic cell rounding.

RhoA is required for cortical retraction and rigidity during mitotic cell rounding.
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DOI:
10.1083/jcb.200207130
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发表时间:
2003-01-20
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Burridge K
Burridge K
中科院分区:
其他
文献类型:
--
作者:
Maddox AS;Burridge K

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有丝分裂细胞变圆是细胞形状改变的过程,其中扁平的间期细胞在有丝分裂开始时变成球形。肌动蛋白细胞骨架的重排、去粘附和皮质硬度的增加伴随有丝分裂细胞变圆。促进这一过程的分子机制尚未确定。我们发现,RhoA是所需的皮质收缩,但不脱粘有丝分裂细胞圆。皮质刚性的有丝分裂增加也需要RhoA,这表明皮质刚性和皮质回缩的增加是相关的过程。Rho激酶也是有丝分裂皮质收缩和刚性所需的,表明RhoA对细胞变圆的影响是通过这种效应器介导的。与RhoA在有丝分裂进入过程中的作用一致,RhoA活性在圆形的有丝分裂前期细胞中升高。RhoA抑制剂p190 RhoGAP的活性由于其丝氨酸/苏氨酸磷酸化而降低。累积起来,这些结果表明,RhoA活性的有丝分裂增加导致皮质肌动蛋白细胞骨架重排,促进皮质硬度,导致有丝分裂细胞变圆。
Mitotic cell rounding is the process of cell shape change in which a flat interphase cell becomes spherical at the onset of mitosis. Rearrangement of the actin cytoskeleton, de-adhesion, and an increase in cortical rigidity accompany mitotic cell rounding. The molecular mechanisms that contribute to this process have not been defined. We show that RhoA is required for cortical retraction but not de-adhesion during mitotic cell rounding. The mitotic increase in cortical rigidity also requires RhoA, suggesting that increases in cortical rigidity and cortical retraction are linked processes. Rho-kinase is also required for mitotic cortical retraction and rigidity, indicating that the effects of RhoA on cell rounding are mediated through this effector. Consistent with a role for RhoA during mitotic entry, RhoA activity is elevated in rounded, preanaphase mitotic cells. The activity of the RhoA inhibitor p190RhoGAP is decreased due to its serine/threonine phosphorylation at this time. Cumulatively, these results suggest that the mitotic increase in RhoA activity leads to rearrangements of the cortical actin cytoskeleton that promote cortical rigidity, resulting in mitotic cell rounding.