CRMP-2 binds to tubulin heterodimers to promote microtubule assembly

Yuko Fukata, Tomohiko J. Itoh, Toshihide Kimura, Celine Ménager, Takashi Nishimura, Takashi Shiromizu, Hiroyasu Watanabe, Naoyuki Inagaki, Akihiro Iwamatsu, Hirokazu Hotani, Kozo Kaibuchi

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561 Citations (Scopus)

Abstract

Regulated increase in the formation of microtubule arrays is thought to be important for axonal growth. Collapsin response mediator protein-2 (CRMP-2) is a mammalian homologue of UNC-33, mutations in which result in abnormal axon termination. We recently demonstrated that CRMP-2 is critical for axonal differentiation. Here, we identify two activities of CRMP-2: tubulin-heterodimer binding and the promotion of microtubule assembly. CRMP-2 bound tubulin dimers with higher affinity than it bound microtubules. Association of CRMP-2 with microtubules was enhanced by tubulin polymerization in the presence of CRMP-2. The binding property of CRMP-2 with tubulin was apparently distinct from that of Tau, which preferentially bound microtubules. In neurons, overexpression of CRMP-2 promoted axonal growth and branching. A mutant of CRMP-2, lacking the region responsible for microtubule assembly, inhibited axonal growth and branching in a dominant-negative manner. Taken together, our results suggest that CRMP-2 regulates axonal growth and branching as a partner of the tubulin heterodimer, in a different fashion from traditional MAPs.

Original languageEnglish
Pages (from-to)583-591
Number of pages9
JournalNature Cell Biology
Volume4
Issue number8
DOIs
Publication statusPublished - 08-2002

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Fukata, Y., Itoh, T. J., Kimura, T., Ménager, C., Nishimura, T., Shiromizu, T., Watanabe, H., Inagaki, N., Iwamatsu, A., Hotani, H., & Kaibuchi, K. (2002). CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nature Cell Biology, 4(8), 583-591. https://doi.org/10.1038/ncb825