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Keywords:

  • gamma-tubulin complexes;
  • microtubule dynamics;
  • mitosis;
  • spindle orientation

Abstract

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.

Synopsis

Thumbnail image of graphical abstract

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.