Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential β-catenin phosphorylation

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

doi:https://doi.org/10.1242/jcs.029660

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2008

Author

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

Suggested citation

David, Mónica Delia; Yeramian Hakim, Andree; Duñach, Mireia; Llovera i Tomàs, Marta; Cantí Nicolás, Carles; Garcia de Herreros, Antonio; ... Herreros Danés, Judit. (2008) . Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential β-catenin phosphorylation. Journal of Cell Science, 2008, vol. 121, núm. 16, p. 2718-2730. https://doi.org/10.1242/jcs.029660.

Abstract

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.

URI

http://hdl.handle.net/10459.1/47340

DOI

https://doi.org/10.1242/jcs.029660

Is part of

Journal of Cell Science, 2008, vol. 121, núm. 16, p. 2718-2730