GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules

Eun Mi Hur, Saijilafu, Byoung Dae Lee, Seong Jin Kim, Wen Lin Xu, Fengquan Zhou

Research output: Contribution to journalArticle

Abstract

Suppression of glycogen synthase kinase 3 (GSK3) activity in neurons yields pleiotropic outcomes, causing both axon growth promotion and inhibition. Previous studies have suggested that specific GSK3 substrates, such as adenomatous polyposis coli (APC) and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs), but the substrate(s) and mechanisms conveying axon growth inhibition remain elusive. Here we show that CLIP (cytoplasmic linker protein)-associated protein (CLASP), originally identified as a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding activity mediates axon growth inhibition induced by suppression of GSK3 activity via preventing MT protrusion into the growth cone periphery, whereas the plus end-binding property supports axon extension via stabilizing the growing ends of axonal MTs. We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs.

Original languageEnglish (US)
Pages (from-to)1968-1981
Number of pages14
JournalGenes & development
Volume25
Issue number18
DOIs
StatePublished - Sep 15 2011

Fingerprint

Glycogen Synthase Kinase 3
Growth Cones
Microtubules
Axons
Growth
Proteins
Adenomatous Polyposis Coli
Carrier Proteins
Neurons

Keywords

  • Developmental and regenerative axon growth
  • Growth cone microtubules
  • GSK3
  • Microtubule plus end-tracking proteins

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules. / Hur, Eun Mi; Saijilafu; Lee, Byoung Dae; Kim, Seong Jin; Xu, Wen Lin; Zhou, Fengquan.

In: Genes & development, Vol. 25, No. 18, 15.09.2011, p. 1968-1981.

Research output: Contribution to journalArticle

Hur, Eun Mi ; Saijilafu ; Lee, Byoung Dae ; Kim, Seong Jin ; Xu, Wen Lin ; Zhou, Fengquan. / GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules. In: Genes & development. 2011 ; Vol. 25, No. 18. pp. 1968-1981.
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