Structural basis for CRMP2-induced axonal microtubule formation

Shinsuke Niwa, Fumio Nakamura, Yuri Tomabechi, Mari Aoki, Hideki Shigematsu, Takashi Matsumoto, Atsushi Yamagata, Shuya Fukai, Nobutaka Hirokawa, Yoshio Goshima, Mikako Shirouzu, Ryo Nitta

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15 Citations (Scopus)

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.

Original languageEnglish
Article number10681
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

ASJC Scopus subject areas

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    Niwa, S., Nakamura, F., Tomabechi, Y., Aoki, M., Shigematsu, H., Matsumoto, T., Yamagata, A., Fukai, S., Hirokawa, N., Goshima, Y., Shirouzu, M., & Nitta, R. (2017). Structural basis for CRMP2-induced axonal microtubule formation. Scientific reports, 7(1), [10681]. https://doi.org/10.1038/s41598-017-11031-4