GSK-3β regulates phosphorylation of CRMP-2 and neuronal polarity

Takeshi Yoshimura, Yoji Kawano, Nariko Arimura, Saeko Kawabata, Akira Kikuchi, Kozo Kaibuchi

Research output: Contribution to journalArticlepeer-review

683 Citations (Scopus)

Abstract

Neurons are highly polarized and comprised of two structurally and functionally distinct parts, an axon and dendrites. We previously showed that collapsin response mediator protein-2 (CRMP-2) is critical for specifying axon/dendrite fate, possibly by promoting neurite elongation via microtubule assembly. Here, we showed that glycogen synthase kinase-3β (GSK-3β) phosphorylated CRMP-2 at Thr-514 and inactivated it. The expression of the nonphosphorylated form of CRMP-2 or inhibition of GSK-3β induced the formation of multiple axon-like neurites in hippocampal neurons. The expression of constitutively active GSK-3β impaired neuronal polarization, whereas the nonphosphorylated form of CRMP-2 counteracted the inhibitory effects of GSK-3β, indicating that GSK-3β regulates neuronal polarity through the phosphorylation of CRMP-2. Treatment of hippocampal neurons with neurotrophin-3 (NT-3) induced inactivation of GSK-3β and dephosphorylation of CRMP-2. Knockdown of CRMP-2 inhibited NT-3-induced axon outgrowth. These results suggest that NT-3 decreases phosphorylated CRMP-2 and increases nonphosphorylated active CRMP-2, thereby promoting axon outgrowth.

Original languageEnglish
Pages (from-to)137-149
Number of pages13
JournalCell
Volume120
Issue number1
DOIs
Publication statusPublished - Jan 14 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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