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

Cell. 2015 Jul 16;162(2):287-299. doi: 10.1016/j.cell.2015.06.014. Epub 2015 Jul 9.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aurora Kinase A / metabolism
  • Autoantigens / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Golgi Apparatus / metabolism*
  • HeLa Cells
  • Humans
  • Karyopherins / metabolism
  • Membrane Proteins / metabolism*
  • Mice
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism
  • Mitosis
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / metabolism
  • Spindle Apparatus
  • Xenopus / metabolism
  • Xenopus Proteins / metabolism

Substances

  • Autoantigens
  • Cell Cycle Proteins
  • Golgin subfamily A member 2
  • Karyopherins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • TPX2 protein, Xenopus
  • TPX2 protein, mouse
  • Xenopus Proteins
  • Aurora Kinase A