Institut Curie, PSL Research University, CNRS UMR 3215, INSERM U934, 75248 Paris, France
Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 3215, INSERM U934, 75005 Paris, France.
J Cell Sci. 2017 Oct 15;130(20):3557-3567. doi: 10.1242/jcs.201350. Epub 2017 Sep 1.
Centrosomes nucleate microtubules and are tightly coupled to the bipolar spindle to ensure genome integrity, cell division orientation and centrosome segregation. While the mechanisms of centrosome-dependent microtubule nucleation and bipolar spindle assembly have been the focus of numerous works, less is known about the mechanisms ensuring the centrosome-spindle coupling. The conserved NuMA protein (Mud in ) is best known for its role in spindle orientation. Here, we analyzed the role of Mud and two of its interactors, Asp and Dynein, in the regulation of centrosome numbers in epithelial cells. We found that Dynein and Mud mainly initiate centrosome-spindle coupling prior to nuclear envelope breakdown (NEB) by promoting correct centrosome positioning or separation, while Asp acts largely independently of Dynein and Mud to maintain centrosome-spindle coupling. Failure in the centrosome-spindle coupling leads to mis-segregation of the two centrosomes into one daughter cell, resulting in cells with supernumerary centrosomes during subsequent divisions. Altogether, we propose that Dynein, Mud and Asp operate sequentially during the cell cycle to ensure efficient centrosome-spindle coupling in mitosis, thereby preventing centrosome mis-segregation to maintain centrosome number.
中心体通过微管核化作用为纺锤体提供两极，从而确保基因组的完整性、细胞分裂的定向性和中心体的分离。虽然中心体依赖性微管核化作用和双极纺锤体组装的机制已经成为众多研究的焦点，但对于确保中心体-纺锤体连接的机制知之甚少。保守的 NuMA 蛋白（Mud in Drosophila）以其在纺锤体定向中的作用而闻名。在这里，我们分析了 Mud 及其两个相互作用蛋白 Asp 和 Dynein 在调控上皮细胞中心体数量中的作用。我们发现，Dynein 和 Mud 在核膜破裂（NEB）之前主要通过促进正确的中心体定位或分离来启动中心体-纺锤体连接，而 Asp 在很大程度上独立于 Dynein 和 Mud 发挥作用，以维持中心体-纺锤体连接。中心体-纺锤体连接的失败导致两个中心体错误地分离到一个子细胞中，导致随后的分裂中细胞出现多余的中心体。总之，我们提出 Dynein、Mud 和 Asp 在细胞周期中顺序作用，以确保有丝分裂中有效的中心体-纺锤体连接，从而防止中心体的错误分离，维持中心体数量。
