Nuclear translocation of the p75 neurotrophin receptor cytoplasmic domain in response to neurotrophin binding
The intracellular domain of the p75 neurotrophin receptor ( p75(ICD)) can be released by gamma-secretase in response to the previous activation of alpha-secretase by phorbol esters. However, ligand-dependent release of p75(ICD) has yet to be described. We show here that nerve growth factor can induc...
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2005 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/156405 |
| Acceso en línea: | http://hdl.handle.net/10261/156405 |
| Access Level: | acceso abierto |
| Palabra clave: | p75NTR γ-secretase regulated intramembrane proteolysis Neurotrophin Nuclear translocation α-secretase |
| Sumario: | The intracellular domain of the p75 neurotrophin receptor ( p75(ICD)) can be released by gamma-secretase in response to the previous activation of alpha-secretase by phorbol esters. However, ligand-dependent release of p75(ICD) has yet to be described. We show here that nerve growth factor can induce the release of p75(ICD) and facilitate its translocation to the nucleus in a gamma-secretase-dependent manner. This effect was observed in RN22 schwannoma cells cultured under serum-free conditions, as well as in Schwann cells, and it was mimicked by other neurotrophins, such as brain-derived neurotrophic factor or neurotrophin-3. Unlike other known examples of regulated intramembrane proteolysis, ligand-dependent release of p75(ICD) did not need the previous activation of alpha-secretase. These results suggest that nuclear translocation of p75(ICD) may represent a novel neurotrophin-mediated signaling pathway. |
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