ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
In vivo regulation of NGF-mediated functions by Nedd4-2 ubiquitination of TrkA.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Multiple glycoforms of TrkA interact with N-cadherin during trigeminal ganglion neurodevelopment.Journal of cell science · 2026Article
- Ndfip2 in TrkA-expressing sensory neurons regulates noxious mechanosensation through control of TrkA signaling and protein levels.Cell death & disease · 2026Article
- Palmitic acid aggravates atopic dermatitis by regulating SGK1/NEDD4L-involved cutaneous neuroimmune inflammation through driving TRPV1 and MRGPRB2 S-palmitoylation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Electroacupuncture Alleviates KOA-Induced Pain and Cartilage Degeneration via NGF/TrkA Pathway.Journal of pain research · 2026Article
- Utility of a commercial antibody against NTRK1 for western blotting and potential application to immunohistochemistry in adult mouse brain.Scientific reports · 2025Article
- NEDD4-2 and the CLC-2 channel regulate neuronal excitability in the pathogenesis of mesial temporal lobe epilepsy.Scientific reports · 2024Article
- Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV.Human molecular genetics · 2023Article
- Enhanced TrkA signaling impairs basal forebrain-dependent behavior.Frontiers in molecular neuroscience · 2023Article
- Review
- Human-Induced Pluripotent Stem Cell-Based Models for Studying Sex-Specific Differences in Neurodegenerative Diseases.Advances in experimental medicine and biology · 2022Review
- γ-Enolase enhances Trk endosomal trafficking and promotes neurite outgrowth in differentiated SH-SY5Y cells.Cell communication and signaling : CCS · 2021Article
- AMPA Receptor Antagonists Facilitate NEDD4-2-Mediated GRIA1 Ubiquitination by Regulating PP2B-ERK1/2-SGK1 Pathway in Chronic Epilepsy Rats.Biomedicines · 2021Article
- microRNA-454-mediated NEDD4-2/TrkA/cAMP axis in heart failure: Mechanisms and cardioprotective implications.Journal of cellular and molecular medicine · 2021Article
- Article
- Tetraspanin1 promotes NGF signaling by controlling TrkA receptor proteostasis.Cellular and molecular life sciences : CMLS · 2020Article
- Feedback regulation of RTK signaling in development.Developmental biology · 2019Review
- Biotinylated Cell-penetrating Peptides to Study Intracellular Protein-protein Interactions.Journal of visualized experiments : JoVE · 2017Article
- Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) Promotes Hippocampus-Dependent Memory via Its Deubiquitinating Effect on TrkB.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- A Review on Ubiquitination of Neurotrophin Receptors: Facts and Perspectives.International journal of molecular sciences · 2017Review
- Epilepsy-associated gene Nedd4-2 mediates neuronal activity and seizure susceptibility through AMPA receptors.PLoS genetics · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
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 remain to 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.