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

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

研究成果: Article査読

710 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)137-149
ページ数13
ジャーナルCell
120
1
DOI
出版ステータスPublished - 14-01-2005
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)

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