Format

Send to

Choose Destination
Sci Rep. 2017 Sep 6;7(1):10681. doi: 10.1038/s41598-017-11031-4.

Structural basis for CRMP2-induced axonal microtubule formation.

Author information

1
Frontier Research Institute for Interdisciplinary Sciences and Department of Life Sciences, Tohoku University, Aoba-ku, Sendai, 980-8578, Japan.
2
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, 236-0004, Japan.
3
Department of Biochemistry, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, 162-8666, Japan.
4
RIKEN Center for Life Science Technologies, Tsurumi-ku, Yokohama, 230-0045, Japan.
5
Application Laboratories, Rigaku Corporation, 3-9-12 Matsubara-Cho, Akishima, Tokyo, 196-8666, Japan.
6
Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0032, Japan.
7
Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan.
8
RIKEN Center for Life Science Technologies, Tsurumi-ku, Yokohama, 230-0045, Japan. ryo.nitta@riken.jp.
9
Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan. ryo.nitta@riken.jp.
10
Division of Structural Medicine and Anatomy, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0017, Japan. ryo.nitta@riken.jp.

Abstract

Microtubule associated protein Collapsin response mediator protein 2 (CRMP2) regulates neuronal polarity in developing neurons through interactions with tubulins or microtubules. However, how CRMP2 promotes axonal formation by affecting microtubule behavior remains unknown. This study aimed to obtain the structural basis for CRMP2-tubulin/microtubule interaction in the course of axonogenesis. The X-ray structural studies indicated that the main interface to the soluble tubulin-dimer is the last helix H19 of CRMP2 that is distinct from the known C-terminal tail-mediated interaction with assembled microtubules. In vitro structural and functional studies also suggested that the H19-mediated interaction promoted the rapid formation of GTP-state microtubules directly, which is an important feature of the axon. Consistently, the H19 mutants disturbed axon elongation in chick neurons, and failed to authorize the structural features for axonal microtubules in Caenorhabditis elegans. Thus, CRMP2 induces effective axonal microtubule formation through H19-mediated interactions with a soluble tubulin-dimer allowing axonogenesis to proceed.

PMID:
28878401
PMCID:
PMC5587665
DOI:
10.1038/s41598-017-11031-4
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center