NME7 is a functional component of the γ-tubulin ring complex

Mol Biol Cell. 2014 Jul 1;25(13):2017-25. doi: 10.1091/mbc.E13-06-0339. Epub 2014 May 7.

Abstract

As the primary microtubule nucleator in animal cells, the γ-tubulin ring complex (γTuRC) plays a crucial role in microtubule organization, but little is known about how the activity of the γTuRC is regulated. Recently, isolated γTuRC was found to contain NME7, a poorly characterized member of the NME family. Here we report that NME7 is a γTuRC component that regulates the microtubule-nucleating activity of the γTuRC. NME7 contains two putative kinase domains, A and B, and shows autophosphorylating activity. Whereas domain A is involved in the autophosphorylation, domain B is inactive. NME7 interacts with the γTuRC through both A and B domains, with Arg-322 in domain B being crucial to the binding. In association with the γTuRC, NME7 localizes to centrosomes throughout the cell cycle and to mitotic spindles during mitosis. Suppression of NME7 expression does not affect γTuRC assembly or localization to centrosomes, but it does impair centrosome-based microtubule nucleation. Of importance, wild-type NME7 promotes γTuRC-dependent nucleation of microtubules, but kinase-deficient NME7 does so only poorly. These results suggest that NME7 functions in the γTuRC in a kinase-dependent manner to facilitate microtubule nucleation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Microtubules / metabolism
  • Molecular Sequence Data
  • Nucleoside-Diphosphate Kinase / chemistry
  • Nucleoside-Diphosphate Kinase / physiology*
  • Phosphorylation
  • Protein Multimerization
  • Protein Processing, Post-Translational
  • Protein Transport
  • Tubulin / chemistry
  • Tubulin / metabolism*

Substances

  • Tubulin
  • NME7 protein, human
  • Nucleoside-Diphosphate Kinase