Axonal growth: where neurotrophins meet Wnts.
Axonal guidance is influenced by many cues, including polypeptide trophic factors, cytokines, diffusible attractants and repellents and changes in calcium. How these signals are conveyed and integrated is not well defined. Recent data suggest that molecules of the canonical Wnt signaling pathway may have direct actions on axonal growth through neurotrophin signaling. This surprising mechanism is supported by local inactivation of glycogen synthase kinase 3beta (GSK-3beta) by nerve growth factor through the integrin-linked kinase. Inhibition of GSK-3beta provides a positive regulatory signal for the cytoskeleton re-arrangement involved in axon extension. Moreover, microtubule stabilization is stimulated by adenomatous polyposis coli protein, a downstream target of GSK3, in response to neurotrophins. Therefore, components of the Wnt signaling pathway are downstream of trophic factors, providing new insights into cytoskeletal regulatory events during axonal growth.
Arévalo
Juan Carlos
JC
Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016 USA. arevalo@saturn.med.nyu.edu
Chao
Moses V
MV
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020439:Growth Cones / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D009420:Nervous System / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins; D000099200:Scaffold Protein ILK
D025601:Adenomatous Polyposis Coli Protein; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D017346:Protein Serine-Threonine Kinases; D051153:Wnt Proteins; D000099200:Scaffold Protein ILK; C000605506:GSK3B protein, human