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Title:
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Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential β-catenin phosphorylation;
ß-catenin phosphorylation by Neurotrophins and Hepatocyte Growth Factor signalling regulates axon morphogenesis
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Author:
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David, Mónica Delia; Yeramian Hakim, Andree; Duñach, Mireia; Llovera i Tomàs, Marta; Cantí Nicolás, Carles; Garcia de Herreros, Antonio; Comella i Carnicé, Joan Xavier; Herreros Danés, Judit
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Notes:
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Tyrosine phosphorylation of ß-catenin, a component of adhesion complexes and the
Wnt pathway, affects cell adhesion, migration and gene transcription. By reducing ßcatenin availability using shRNA-mediated gene silencing or expression of intracellular N-cadherin, we show that ß-catenin is required for axon growth downstream of Brain Derived Neurotrophic Factor (BDNF) and Hepatocyte Growth Factor (HGF) signalling.
We demonstrate that receptor tyrosine kinases (RTK) Trk and Met interact with and
phosphorylate ß-catenin. Neurotrophins (NT) stimulation of Trk receptors results in
phosphorylation of ß-catenin at residue Y654 and increased axon growth and
branching. Conversely, pharmacological inhibition of Trk or a Y654F mutant blocks
these effects. ß-catenin phospho(P)-Y654 colocalizes with the cytoskeleton at growth cones. However, HGF that also increases axon growth and branching, induces ß-catenin phosphorylation at Y142 and a nuclear localization. Interestingly, dominant negative ΔN-TCF4 abolishes the effects of HGF in axon growth and branching, but not of NT.
We conclude that NT and HGF signalling differentially phosphorylate ß-catenin,
targeting ß-catenin to distinct compartments to regulate axon morphogenesis by TCF4-transcription-dependent and independent mechanisms. These results place ß-catenin downstream of growth factor/RTK signalling in axon differentiation. |
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Subject(s):
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-β-catenin
-Neurotrophins
-Hepatocyte growth factor
-Axon growth
-Sistema nerviós
-Axons |
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Rights:
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(c) Company of Biologists, 2008
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Document type:
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article
acceptedVersion |
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Published by:
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Company of Biologist
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