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P75 neurotrophin receptor reduces ligand-induced Trk receptor ubiquitination and delays Trk receptor internalization and degradation.

ABSTRACT: Target-derived neurotrophins regulate neuronal survival and growth by interacting with cell-surface tyrosine kinase receptors. The p75 neurotrophin receptor (p75 NTR) is coexpressed with Trk receptors in long-range projection neurons, in which it facilitates neurotrophin binding to Trk and enhances Trk activity. Here, we show that TrkA and TrkB receptors undergo robust ligand-dependent ubiquitination that is dependent on activation of the endogenous Trk activity of the receptors. Coexpression of p75 NTR attenuated ubiquitination of TrkA and TrkB and delayed nerve growth factor-induced TrkA receptor internalization and receptor degradation. These results indicate that p75 NTR may prolong cell-surface Trk-dependent signalling events by negatively regulating receptor ubiquitination.

SUBMITTER: Makkerh JP

PROVIDER: S-EPMC1369184 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature

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p75 neurotrophin receptor reduces ligand-induced Trk receptor ubiquitination and delays Trk receptor internalization and degradation.

Makkerh Joe P S JP Ceni Claire C Auld Daniel S DS Vaillancourt François F Dorval Genevieve G Barker Philip A PA

EMBO reports 20051001 10

Target-derived neurotrophins regulate neuronal survival and growth by interacting with cell-surface tyrosine kinase receptors. The p75 neurotrophin receptor (p75 NTR) is coexpressed with Trk receptors in long-range projection neurons, in which it facilitates neurotrophin binding to Trk and enhances Trk activity. Here, we show that TrkA and TrkB receptors undergo robust ligand-dependent ubiquitination that is dependent on activation of the endogenous Trk activity of the receptors. Coexpression of ...[more]

PMID: 16113645

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