Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Cell. 2013 Jul 18;154(2):391-402. doi: 10.1016/j.cell.2013.06.010.
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.
有丝分裂纺锤体的位置决定了细胞在胞质分裂过程中的分裂部位。然而，控制纺锤体定位以产生大小均等的子细胞的机制仍知之甚少。在这里，我们证明了两种机制在人类对称分裂细胞的后期中协同作用以将纺锤体定位于中心。首先，纺锤体直接由基于微管的马达蛋白 dynein 定位，我们证明 dynein 通过两条不同的途径被靶向到质膜：一种是 Gαi/LGN/NuMA 依赖性途径，另一种是 4.1G/R 和 NuMA 依赖性、后期特异性途径。其次，我们发现不对称的质膜延伸是对纺锤体定位错误的反应，以改变相对于纺锤体的细胞边界。不对称的膜延伸是由染色体衍生的 Ran-GTP 信号促进的，该信号局部减少生长质膜处的 Anillin。在不对称伸长的细胞中，固定质膜处 dynein 依赖性的纺锤体锚定确保了纺锤体的正确定位。我们的研究结果揭示了实现均等细胞分裂的后期特异性纺锤体定位系统。
