TY - JOUR
T1 - GM130 Regulates Golgi-Derived Spindle Assembly by Activating TPX2 and Capturing Microtubules
AU - Wei, Jen Hsuan
AU - Zhang, Zi Chao
AU - Wynn, R. Max
AU - Seemann, Joachim
N1 - Funding Information:
We thank Rebecca Heald and Kara Helmke for insightful discussion and support during project development, Matthew Beard for GM130 constructs, Yuh Min Chook for importin constructs, Luke Rice for Mal3 protein, and Beatriz Fontoura for suggestions. This work is supported by the NIH grant GM096070 to J.S.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/7/18
Y1 - 2015/7/18
N2 - Summary 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.
AB - Summary 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.
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U2 - 10.1016/j.cell.2015.06.014
DO - 10.1016/j.cell.2015.06.014
M3 - Article
C2 - 26165940
AN - SCOPUS:84937250948
SN - 0092-8674
VL - 162
SP - 287
EP - 299
JO - Cell
JF - Cell
IS - 2
M1 - 8260
ER -