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

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dc.contributor.authorDavid, Mónica Delia
dc.contributor.authorYeramian Hakim, Andree
dc.contributor.authorDuñach, Mireia
dc.contributor.authorLlovera i Tomàs, Marta
dc.contributor.authorCantí Nicolás, Carles
dc.contributor.authorGarcia de Herreros, Antonio
dc.contributor.authorComella i Carnicé, Joan Xavier
dc.contributor.authorHerreros Danés, Judit
dc.date.accessioned2014-06-20T14:23:25Z
dc.date.available2014-06-20T14:23:25Z
dc.date.issued2008
dc.description.abstractTyrosine 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.ca_ES
dc.identifier.doihttps://doi.org/10.1242/jcs.029660
dc.identifier.idgrec011261
dc.identifier.issn0021-9533
dc.identifier.urihttp://hdl.handle.net/10459.1/47340
dc.language.isoengca_ES
dc.publisherCompany of Biologistca_ES
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1242/jcs.029660ca_ES
dc.relation.ispartofJournal of Cell Science, 2008, vol. 121, núm. 16, p. 2718-2730ca_ES
dc.rights(c) Company of Biologists, 2008ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.subjectβ-catenin
dc.subjectNeurotrophins
dc.subjectHepatocyte growth factor
dc.subjectAxon growth
dc.subject.otherSistema nerviósca_ES
dc.subject.otherAxonsca_ES
dc.titleSignalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential β-catenin phosphorylationca_ES
dc.title.alternativeß-catenin phosphorylation by Neurotrophins and Hepatocyte Growth Factor signalling regulates axon morphogenesis
dc.typearticleca_ES
dc.type.versionacceptedVersionca_ES
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