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Nuclear translocation of the p75 neurotrophin receptor cytoplasmic domain in response to neurotrophin binding.

ABSTRACT: The intracellular domain of the p75 neurotrophin receptor (p75ICD) can be released by gamma-secretase in response to the previous activation of alpha-secretase by phorbol esters. However, ligand-dependent release of p75ICD has yet to be described. We show here that nerve growth factor can induce the release of p75ICD 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 p75ICD did not need the previous activation of alpha-secretase. These results suggest that nuclear translocation of p75ICD may represent a novel neurotrophin-mediated signaling pathway.

SUBMITTER: Frade JM

PROVIDER: S-EPMC6726010 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature

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Nuclear translocation of the p75 neurotrophin receptor cytoplasmic domain in response to neurotrophin binding.

Frade José M JM

The Journal of neuroscience : the official journal of the Society for Neuroscience 20050201 6

The intracellular domain of the p75 neurotrophin receptor (p75ICD) can be released by gamma-secretase in response to the previous activation of alpha-secretase by phorbol esters. However, ligand-dependent release of p75ICD has yet to be described. We show here that nerve growth factor can induce the release of p75ICD 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 wel ...[more]

PMID: 15703394

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