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

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

Author information

1
1] Molecular Cellular Biology Laboratory, Yokohama City University, Graduate School of Medical Science, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Department of Molecular Biology, Yokohama City University, Graduate School of Medical Science, 3-9, Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
2
Molecular Cellular Biology Laboratory, Yokohama City University, Graduate School of Medical Science, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
3
Faculty of Pharmaceutical Sciences, Teikyo Heisei University, 4-21-2 Nakano, Nakano-ku, Tokyo 164-8530, Japan.
4
Electron Microscope Laboratory, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
5
Molecular Medical Bioscience Laboratory, Yokohama City University, Graduate School of Medical Life Science, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
6
Department of Molecular Biology, Yokohama City University, Graduate School of Medical Science, 3-9, Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.

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.

PMID:
25366663
DOI:
10.1038/ncomms6266
[Indexed for MEDLINE]

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