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dc.contributor.authorGeorgieva, Maya V.
dc.contributor.authorPablo Llavall, Yolanda de
dc.contributor.authorSanchis, Daniel
dc.contributor.authorComella i Carnicé, Joan Xavier
dc.contributor.authorLlovera i Tomàs, Marta
dc.date.accessioned2016-06-01T08:30:17Z
dc.date.issued2011
dc.identifier.issn0022-3042
dc.identifier.urihttp://hdl.handle.net/10459.1/57138
dc.description.abstractThe nerve growth factor receptor TrkA (tropomyosin-related kinase receptor) participates in the survival and differentiation of several neuronal populations. The C-terminal tail of TrkA contains a PPXY motif, the binding site of the E3 ubiquitinligase Nedd4-2 (neural precursor cell expressed, developmentally down-regulated 4-2). In order to analyze the role of Nedd4-2 ubiquitination on TrkA function, we generated three TrkA mutants, by introducing point mutations on conserved hydrophobic amino acids – Leu784 and Val790 switched to Ala. TrkA mutants co-localized and co-immunoprecipitated more efficiently with Nedd4-2 and consequently a strong increase in the basal multimonoubiquitination of the mutant receptors was observed. In addition, we found a decrease in TrkA abundance because of the preferential sorting of mutant receptors towards the late endosome/lysosome pathway instead of recycling back to the plasma membrane. Despite the reduction in the amount of membrane receptor caused by the C-terminal changes, TrkA mutants were able to activate signaling cascades and were even more efficient in promoting neurite outgrowth than the wild-type receptor. Our results demonstrate that the C-terminal tail hydrophobicity of TrkA regulates Nedd4-2 binding and activity and therefore controls receptor turnover. In addition, TrkA multimonoubiquitination does not interfere with the activation of signaling cascades, but rather potentiates receptor signaling leading to differentiation.ca_ES
dc.description.sponsorshipThe work was supported by the Instituto de Salud Carlos III – Ministerio de Sanidad y Consumo (FIS) (PI04/2537 and PS09/ 00140) to ML, the Ministry of Science and Innovation of Spain (SAF2005-02197 and SAF2008-02271) to DS and SAF2007-60287, Programa de Suport a Grups de Recerca from the Government of Catalonia (SGR2005-00628) and Ciberned (CB06/05/1104) to JXC. MVG is supported by ‘Departament d’Universitat, Recerca i Societat de la Informacio’ (DURSI) and the European Social Fund from the Government of Catalonia (DIUE).ca_ES
dc.language.isoengca_ES
dc.publisherWileyca_ES
dc.relationMIECI/PN2004-2007/SAF2005-02197
dc.relationMICINN/PN2008-2011/SAF2008-02271
dc.relationMIECI/PN2004-2007/SAF2007-60287
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1111/j.1471-4159.2011.07218.xca_ES
dc.relation.ispartofJournal of Neurochemistry, 2011, vol. 117, núm. 3ca_ES
dc.rights(c) Wiley, 2011ca_ES
dc.subjectDegradationca_ES
dc.subjectDifferentiationca_ES
dc.subjectNeurotrophin receptorca_ES
dc.titleUbiquitination of TrkA by Nedd4-2 regulates receptor lysosomal targeting and mediates receptor signalingca_ES
dc.typearticleca_ES
dc.identifier.idgrec017839
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1111/j.1471-4159.2011.07218.x
dc.date.embargoEndDate10000-01-01


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