Wei Jen-Hsuan, Zhang Zi Chao, Wynn R Max, Seemann Joachim
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell. 2015 Jul 16;162(2):287-299. doi: 10.1016/j.cell.2015.06.014. Epub 2015 Jul 9.
Spindle assembly requires the coordinated action of multiple cellular structures to nucleate and organize microtubules in a precise spatiotemporal manner. Among them, the contributions of centrosomes, chromosomes, and microtubules have been well studied, yet the involvement of membrane-bound organelles remains largely elusive. Here, we provide mechanistic evidence for a membrane-based, Golgi-derived microtubule assembly pathway in mitosis. Upon mitotic entry, the Golgi matrix protein GM130 interacts with importin α via a classical nuclear localization signal that recruits importin α to the Golgi membranes. Sequestration of importin α by GM130 liberates the spindle assembly factor TPX2, which activates Aurora-A kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GM130, thus linking Golgi membranes to the spindle. Our results reveal an active role for the Golgi in regulating spindle formation to ensure faithful organelle inheritance.
纺锤体组装需要多种细胞结构协同作用,以精确的时空方式使微管成核并进行组织。其中,中心体、染色体和微管的作用已得到充分研究,但膜结合细胞器的参与情况仍 largely 难以捉摸。在这里,我们提供了有丝分裂中基于膜的、源自高尔基体的微管组装途径的机制证据。在有丝分裂开始时,高尔基体基质蛋白 GM130 通过经典的核定位信号与输入蛋白 α 相互作用,该信号将输入蛋白 α 招募到高尔基体膜上。GM130 对输入蛋白 α 的隔离释放了纺锤体组装因子 TPX2,TPX2 激活极光激酶 A 并刺激局部微管成核。在细丝组装时,新生微管被 GM130 进一步捕获,从而将高尔基体膜与纺锤体相连。我们的结果揭示了高尔基体在调节纺锤体形成以确保细胞器忠实遗传方面的积极作用。