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

Eun-Mi Hur1, Saijilafu, Byoung Dae Lee

  • 1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Genes & Development
|September 23, 2011
PubMed

Insights

Suppression of glycogen synthase kinase 3 (GSK3) impacts neuron axon growth. CLASP protein

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Glycogen synthase kinase 3 (GSK3) activity in neurons has complex effects on axon growth, promoting some aspects while inhibiting others.
  • Previous research identified GSK3 substrates like APC and CRMP2 involved in axon growth via microtubule (MT) stabilization, but mechanisms for growth inhibition are unclear.

Purpose of the Study:

  • To elucidate the substrates and mechanisms by which GSK3 suppression leads to axon growth inhibition.
  • To investigate the role of CLIP-associated protein (CLASP) in mediating the opposing effects of GSK3 activity on axon growth.

Main Methods:

  • Investigated the dual MT-binding activities (plus end-binding and lattice-binding) of CLASP in neuronal growth cones.
  • Examined how these CLASP activities correlate with axon growth promotion and inhibition under varying GSK3 activity levels.

Main Results:

  • CLASP exhibits both plus end-binding and lattice-binding activities within the growth cone MT network.
  • CLASP's lattice-binding activity inhibits axon growth by preventing MT protrusion, while its plus end-binding activity promotes growth by stabilizing MT ends.
  • These opposing CLASP functions are modulated by GSK3 activity levels.

Conclusions:

  • CLASP acts as a key mediator, translating GSK3 activity into differential regulation of axon growth.
  • The study proposes a model where CLASP coordinates MT stability and configuration in the growth cone to control axon extension.
  • Understanding CLASP's dual role offers insights into neuronal development and potential therapeutic targets.

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