Essential Roles for GSK-3s and GSK-3-Primed Substrates in Neurotrophin-Induced and Hippocampal Axon Growth

Woo Yang Kim, Feng Quan Zhou, Jiang Zhou, Yukako Yokota, Yan Min Wang, Takeshi Yoshimura, Kozo Kaibuchi, James R R. Woodgett, E. S. Anton, William D D. Snider

研究成果: Article査読

182 被引用数 (Scopus)

抄録

Glycogen synthase kinase-3β (GSK-3β) is thought to mediate morphological responses to a variety of extracellular signals. Surprisingly, we found no gross morphological deficits in nervous system development in GSK-3β null mice. We therefore designed an shRNA that targeted both GSK-3 isoforms. Strong knockdown of both GSK-3α and β markedly reduced axon growth in dissociated cultures and slice preparations. We then assessed the role of different GSK-3 substrates in regulating axon morphology. Elimination of activity toward primed substrates only using the GSK-3 R96A mutant was associated with a defect in axon polarity (axon branching) compared to an overall reduction in axon growth induced by a kinase-dead mutant. Consistent with this finding, moderate reduction of GSK-3 activity by pharmacological inhibitors induced axon branching and was associated primarily with effects on primed substrates. Our results suggest that GSK-3 is a downstream convergent point for many axon growth regulatory pathways and that differential regulation of primed versus all GSK-3 substrates is associated with a specific morphological outcome.

本文言語English
ページ(範囲)981-996
ページ数16
ジャーナルNeuron
52
6
DOI
出版ステータスPublished - 21-12-2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)

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