MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane

Nat Commun. 2014 Nov 4;5:5266. doi: 10.1038/ncomms6266.

Abstract

Recent studies have revealed the presence of a microtubule subpopulation called Golgi-derived microtubules that support Golgi ribbon formation, which is required for maintaining polarized cell migration. CLASPs and AKAP450/CG-NAP are involved in their formation, but the underlying molecular mechanisms remain unclear. Here, we find that the microtubule-crosslinking protein, MTCL1, is recruited to the Golgi membranes through interactions with CLASPs and AKAP450/CG-NAP, and promotes microtubule growth from the Golgi membrane. Correspondingly, MTCL1 knockdown specifically impairs the formation of the stable perinuclear microtubule network to which the Golgi ribbon tethers and extends. Rescue experiments demonstrate that besides its crosslinking activity mediated by the N-terminal microtubule-binding region, the C-terminal microtubule-binding region plays essential roles in these MTCL1 functions through a novel microtubule-stabilizing activity. These results suggest that MTCL1 cooperates with CLASPs and AKAP450/CG-NAP in the formation of the Golgi-derived microtubules, and mediates their development into a stable microtubule network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A Kinase Anchor Proteins / metabolism
  • Animals
  • Cytoskeletal Proteins / metabolism
  • Gene Knockdown Techniques
  • Golgi Apparatus / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Membranes / metabolism*
  • Mice
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Rabbits
  • Rats

Substances

  • A Kinase Anchor Proteins
  • AKAP9 protein, human
  • Cytoskeletal Proteins
  • MTCL1 protein, human
  • Microtubule-Associated Proteins