MRC Laboratory for Molecular Cell Biology, University College London, Gower St., London WC1E 6BT, UK.
Dev Cell. 2012 Aug 14;23(2):371-83. doi: 10.1016/j.devcel.2012.06.003.
As they enter mitosis, animal cells undergo profound actin-dependent changes in shape to become round. Here we identify the Cdk1 substrate, Ect2, as a central regulator of mitotic rounding, thus uncovering a link between the cell-cycle machinery that drives mitotic entry and its accompanying actin remodeling. Ect2 is a RhoGEF that plays a well-established role in formation of the actomyosin contractile ring at mitotic exit, through the local activation of RhoA. We find that Ect2 first becomes active in prophase, when it is exported from the nucleus into the cytoplasm, activating RhoA to induce the formation of a mechanically stiff and rounded metaphase cortex. Then, at anaphase, binding to RacGAP1 at the spindle midzone repositions Ect2 to induce local actomyosin ring formation. Ect2 localization therefore defines the stage-specific changes in actin cortex organization critical for accurate cell division.
当动物细胞进入有丝分裂时,它们会发生深刻的肌动蛋白依赖性形态变化,变成圆形。在这里,我们确定 Cdk1 底物 Ect2 是有丝分裂圆形化的核心调节剂,从而揭示了驱动有丝分裂进入的细胞周期机制与其伴随的肌动蛋白重塑之间的联系。Ect2 是一种 RhoGEF,它在有丝分裂后期通过局部激活 RhoA 在肌动球蛋白收缩环的形成中起着重要作用。我们发现 Ect2 在前期首先变得活跃,此时它从细胞核输出到细胞质中,激活 RhoA 诱导机械刚性和圆形中期皮质的形成。然后,在后期,Ect2 与纺锤体中部的 RacGAP1 结合,重新定位以诱导局部肌动球蛋白环的形成。因此,Ect2 的定位定义了有丝分裂过程中肌动蛋白皮质组织的特定阶段变化,这对于准确的细胞分裂至关重要。