γ-Tubulin Ring Complexes and EB1 play antagonistic roles in microtubule dynamics and spindle positioning
Article first published online: 14 JAN 2014
© 2014 The Authors
The EMBO Journal
Volume 33, Issue 2, pages 114–128, 16 January 2014
How to Cite
EMBO Journal (2014) 33, 114–128
- Issue published online: 14 JAN 2014
- Article first published online: 14 JAN 2014
- Manuscript Accepted: 16 OCT 2013
- Manuscript Revised: 2 OCT 2013
- Manuscript Received: 12 JUN 2013
- Association pour la Recherche sur le Cancer. Grant Numbers: 4720XP0230F, 1094
- Centre National de la Recherche Scientifique
- Pierre Fabre Laboratories
- Fonds Européens de Développement Economique Régional
- gamma-tubulin complexes;
- microtubule dynamics;
- spindle orientation
γ-Tubulin is critical for microtubule (MT) assembly and organization. In metazoa, this protein acts in multiprotein complexes called γ-Tubulin Ring Complexes (γ-TuRCs). While the subunits that constitute γ-Tubulin Small Complexes (γ-TuSCs), the core of the MT nucleation machinery, are essential, mutation of γ-TuRC-specific proteins in Drosophila causes sterility and morphological abnormalities via hitherto unidentified mechanisms. Here, we demonstrate a role of γ-TuRCs in controlling spindle orientation independent of MT nucleation activity, both in cultured cells and in vivo, and examine a potential function for γ-TuRCs on astral MTs. γ-TuRCs locate along the length of astral MTs, and depletion of γ-TuRC-specific proteins increases MT dynamics and causes the plus-end tracking protein EB1 to redistribute along MTs. Moreover, suppression of MT dynamics through drug treatment or EB1 down-regulation rescues spindle orientation defects induced by γ-TuRC depletion. Therefore, we propose a role for γ-TuRCs in regulating spindle positioning by controlling the stability of astral MTs.
γ-TuRCs gain an unexpected mitotic function in stabilizing astral microtubules, independent of their essential microtubule nucleation roles at centrosomes
- γ-TuRCs are shown to be involved in spindle positioning both in cultured cells and during asymmetric divisions of Drosophila neuroblasts.
- γ-TuRCs associated to astral microtubules control spindle positioning by regulating microtubule dynamics.
- Spindle positioning defects in γ-TuRC-depleted cells are rescued by suppressing microtubule dynamics.
- An antagonism is shown between EB1 and γ-TuRCs, on controlling spindle size and orientation.