GM130 Regulates Golgi-Derived Spindle Assembly by Activating TPX2 and Capturing Microtubules

被引:96
作者
Wei, Jen-Hsuan [1 ]
Zhang, Zi Chao [2 ]
Wynn, R. Max [3 ]
Seemann, Joachim [1 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA
[3] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
关键词
MATRIX PROTEIN GM130; MITOTIC SPINDLE; IMPORTIN-ALPHA; HELA-CELLS; AURORA-A; RAN; NUCLEATION; APPARATUS; MITOSIS; COMPLEX;
D O I
10.1016/j.cell.2015.06.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Spindle assembly requires the coordinated action of multiple cellular structures to nucleate and organize microtubules in a precise spatiotemporal manner. Amongthem, 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 alpha via a classical nuclear localization signal that recruits importin alpha to the Golgi membranes. Sequestration of importin alpha 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.
引用
收藏
页码:287 / 299
页数:13
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