Phosphorylation by Rho kinase regulates CRMP-2 activity in growth cones

Nariko Arimura, Céline Ménager, Yoji Kawano, Takeshi Yoshimura, Saeko Kawabata, Atsushi Hattori, Yuko Fukata, Mutsuki Amano, Yoshio Goshima, Masaki Inagaki, Nobuhiro Morone, Jiro Usukura, Kozo Kaibuchi

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192 Citations (Scopus)

Abstract

Collapsin response mediator protein 2 (CRMP-2) enhances the advance of growth cones by regulating microtubule assembly and Numb-mediated endocytosis. We previously showed that Rho kinase phosphorylates CRMP-2 during growth cone collapse; however, the roles of phosphorylated CRMP-2 in growth cone collapse remain to be clarified. Here, we report that CRMP-2 phosphorylation by Rho kinase cancels the binding activity to the tubulin dimer, microtubules, or Numb. CRMP-2 binds to actin, but its binding is not affected by phosphorylation. Electron microscopy revealed that CRMP-2 localizes on microtubules, clathrin-coated pits, and actin filaments in dorsal root ganglion neuron growth cones, while phosphorylated CRMP-2 localizes only on actin filaments. The phosphomimic mutant of CRMP-2 has a weakened ability to enhance neurite elongation. Furthermore, ephrin-A5 induces phosphorylation of CRMP-2 via Rho kinase during growth cone collapse. Taken together, these results suggest that Rho kinase phosphorylates CRMP-2, and inactivates the ability of CRMP-2 to promote microtubule assembly and Numb-mediated endocytosis, during growth cone collapse.

Original languageEnglish
Pages (from-to)9973-9984
Number of pages12
JournalMolecular and Cellular Biology
Volume25
Issue number22
DOIs
Publication statusPublished - Nov 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Arimura, N., Ménager, C., Kawano, Y., Yoshimura, T., Kawabata, S., Hattori, A., Fukata, Y., Amano, M., Goshima, Y., Inagaki, M., Morone, N., Usukura, J., & Kaibuchi, K. (2005). Phosphorylation by Rho kinase regulates CRMP-2 activity in growth cones. Molecular and Cellular Biology, 25(22), 9973-9984. https://doi.org/10.1128/MCB.25.22.9973-9984.2005