In VivoRegulation of NGF-Mediated Functions by Nedd4-2 Ubiquitination of TrkA
[EN]Trk neurotrophin receptor ubiquitination in response to ligand activation regulates signaling, trafficking, and degradation of the receptors.However,the in vivo consequences of Trk ubiquitination remainto be addressed.We have developed a mouse model with a mutation in the TrkA neurotrophin recep...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/163147 |
| Acceso en línea: | http://hdl.handle.net/10366/163147 |
| Access Level: | acceso abierto |
| Palabra clave: | neurotrophins pain TrkA neurotrophin receptor ubiquitination Pain Receptor, trkA Neurotrophin 3 Ubiquitination 2490 Neurociencias neurotrofina 3 receptor trkA dolor ubicuitinación |
| Sumario: | [EN]Trk neurotrophin receptor ubiquitination in response to ligand activation regulates signaling, trafficking, and degradation of the receptors.However,the in vivo consequences of Trk ubiquitination remainto be addressed.We have developed a mouse model with a mutation in the TrkA neurotrophin receptor (P782S) that results in reduced ubiquitination due to a lack of binding to the E3 ubiquitin ligase, Nedd4-2. In vivo analyses of TrkAP782S indicate that defective ubiquitination of the TrkA mutant results in an altered trafficking and degradation of the receptor that affects the survival of sensory neurons. The dorsal root ganglia from the TrkAP782S knock-in mice display an increased number of neurons expressing CGRP and substance P. Moreover, the mutant mice show enhanced sensitivity to thermal and inflammatory pain. Our results indicate that the ubiquitination of the TrkA neurotrophin receptor plays a critical role in NGF-mediated functions, such as neuronal survival and sensitivity to pain. |
|---|