Cortical Dynein and Asymmetric Membrane Elongation Coordinately Position the Spindle in Anaphase
Cortical Dynein and Asymmetric Membrane Elongation Coordinately Position the Spindle in Anaphase
复制标题
DOI：
10.1016/j.cell.2013.08.036
复制
发表时间：
2013
期刊：
影响因子：
64.5
通讯作者：
Tomomi Kiyomitsu;I. Cheeseman
中科院分区：
文献类型：
--
作者：
Tomomi Kiyomitsu;I. Cheeseman
有丝分裂纺锤体的位置决定了胞质分裂时的细胞分裂位点。然而，控制纺锤体定位以产生相等大小的子细胞的机制仍然知之甚少。在这里，我们证明了两种机制协调行动，以中心的纺锤体在后期对称分裂的人类细胞。首先，纺锤体直接由基于微管的运动动力蛋白定位，我们证明它通过两种不同的途径靶向细胞皮质：Gαi/LGN/NuMA依赖性途径和4.1G/R和NuMA依赖性的后期特异性途径。其次，我们发现，不对称的质膜伸长发生在响应纺锤体错位改变细胞边界相对于纺锤体。染色体衍生的Ran-GTP信号促进不对称膜伸长，该信号在生长的细胞皮质局部减少苯胺。在不对称伸长的细胞中，动力蛋白依赖的纺锤体锚定在静止的细胞皮层，确保了正确的纺锤体定位。我们的结果揭示了后期特异性纺锤体定中心系统，可实现等大小的细胞分裂。
Mitotic spindle position defines the cell-cleavage site during cytokinesis. However, the mechanisms that control spindle positioning to generate equal-sized daughter cells remain poorly understood. Here, we demonstrate that two mechanisms act coordinately to center the spindle during anaphase in symmetrically dividing human cells. First, the spindle is positioned directly by the microtubule-based motor dynein, which we demonstrate is targeted to the cell cortex by two distinct pathways: a Gαi/LGN/NuMA-dependent pathway and a 4.1G/R and NuMA-dependent, anaphase-specific pathway. Second, we find that asymmetric plasma membrane elongation occurs in response to spindle mispositioning to alter the cellular boundaries relative to the spindle. Asymmetric membrane elongation is promoted by chromosome-derived Ran-GTP signals that locally reduce Anillin at the growing cell cortex. In asymmetrically elongating cells, dynein-dependent spindle anchoring at the stationary cell cortex ensures proper spindle positioning. Our results reveal the anaphase-specific spindle centering systems that achieve equal-sized cell division.