TrkA receptor activation by nerve growth factor induces shedding of the p75 neurotrophin receptor followed by endosomal gamma-secretase-mediated release of the p75 intracellular domain

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dc.contributor.authorUrra, Soledad
dc.contributor.authorEscudero, Claudia A.
dc.contributor.authorRamos, Patricio
dc.contributor.authorLisbona, Fernanda
dc.contributor.authorAllende, Edgardo
dc.contributor.authorCovarrubias, Paulina
dc.contributor.authorParraguez, Jose I.
dc.contributor.authorZampieri, Niccolo
dc.contributor.authorChao, Moses V.
dc.contributor.authorAnnaert, Wim
dc.contributor.authorBronfman, Francisca C.
dc.date.accessioned2024-01-10T13:44:02Z
dc.date.available2024-01-10T13:44:02Z
dc.date.issued2007
dc.description.abstractNeurotrophins are trophic factors that regulate important neuronal functions. They bind two unrelated receptors, the Trk family of receptor-tyrosine kinases and the p75 neurotrophin receptor (p75). p75 was recently identified as a new substrate for gamma-secretase-mediated intramembrane proteolysis, generating a p75-derived intracellular domain (p75-ICD) with signaling capabilities. Using PC12 cells as a model, we studied how neurotrophins activate p75 processing and where these events occur in the cell. We demonstrate that activation of the TrkA receptor upon binding of nerve growth factor (NGF) regulates the metalloprotease-mediated shedding of p75 leaving a membrane-bound p75 C-terminal fragment (p75-CTF). Using subcellular fractionation to isolate a highly purified endosomal fraction, we demonstrate that p75-CTF ends up in endosomes where gamma-secretase-mediated p75-CTF cleavage occurs, resulting in the release of a p75-ICD. Moreover, we show similar structural requirements for gamma-secretase processing of p75 and amyloid precursor protein-derived CTFs. Thus, NGF-induced endocytosis regulates both signaling and proteolytic processing of p75.
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent10 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1074/jbc.M610458200
dc.identifier.eissn1083-351X
dc.identifier.pubmedidMEDLINE:17215246
dc.identifier.urihttps://doi.org/10.1074/jbc.M610458200
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78822
dc.identifier.wosidWOS:000245080900073
dc.information.autorucBachillerato;Allende E;S/I;121020
dc.information.autorucCiencias Biológicas;Bronfman F;S/I;86829
dc.information.autorucBachillerato;Covarrubias MP;S/I;119732
dc.information.autorucBachillerato;Escudero CA;S/I;3761
dc.information.autorucCiencias Biológicas;Urra MS;S/I;112690
dc.issue.numero10
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final7615
dc.pagina.inicio7606
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.revistaJOURNAL OF BIOLOGICAL CHEMISTRY
dc.rightsacceso abierto
dc.subjectAMYLOID PRECURSOR PROTEIN
dc.subjectREGULATED INTRAMEMBRANE PROTEOLYSIS
dc.subjectALPHA-CONVERTING-ENZYME
dc.subjectALZHEIMERS-DISEASE
dc.subjectNUCLEAR TRANSLOCATION
dc.subjectRETROGRADE TRANSPORT
dc.subjectSYMPATHETIC NEURONS
dc.subjectTERMINAL FRAGMENT
dc.subjectTRANSGENIC MICE
dc.subjectBETA PRODUCTION
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleTrkA receptor activation by nerve growth factor induces shedding of the p75 neurotrophin receptor followed by endosomal gamma-secretase-mediated release of the p75 intracellular domain
dc.typeartículo
dc.volumen282
sipa.codpersvinculados121020
sipa.codpersvinculados86829
sipa.codpersvinculados119732
sipa.codpersvinculados3761
sipa.codpersvinculados112690
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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