The ubiquitin ligase MYCBP2 regulates transient receptor potential vanilloid receptor 1 (TRPV1) internalization through inhibition of p38 MAPK signaling

  • The E3 ubiquitin ligase MYCBP2 negatively regulates neuronal growth, synaptogenesis, and synaptic strength. More recently it was shown that MYCBP2 is also involved in receptor and ion channel internalization. We found that mice with a MYCBP2-deficiency in peripheral sensory neurons show prolonged thermal hyperalgesia. Loss of MYCBP2 constitutively activated p38 MAPK and increased expression of several proteins involved in receptor trafficking. Surprisingly, loss of MYCBP2 inhibited internalization of transient receptor potential vanilloid receptor 1 (TRPV1) and prevented desensitization of capsaicin-induced calcium increases. Lack of desensitization, TRPV internalization and prolonged hyperalgesia were reversed by inhibition of p38 MAPK. The effects were TRPV-specific, since neither mustard oil-induced desensitization nor behavioral responses to mechanical stimuli were affected. In summary, we show here for the first time that p38 MAPK activation can inhibit activity-induced ion channel internalization and that MYCBP2 regulates internalization of TRPV1 in peripheral sensory neurons as well as duration of thermal hyperalgesia through p38 MAPK.

Export metadata

Additional Services

Share in Twitter Search Google Scholar
Metadaten
Author:Sabrina Marion HollandORCiDGND, Ovidiu Coste, Dong Dong Zhang, Sandra C. PierreORCiD, Gerd GeisslingerORCiDGND, Klaus ScholichORCiD
URN:urn:nbn:de:hebis:30:3-765621
DOI:https://doi.org/10.1074/jbc.M110.154765
ISSN:0021-9258
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/21098484
Parent Title (English):Journal of biological chemistry
Publisher:American Society for Biochemistry and Molecular Biology Publications
Place of publication:Bethesda, Md
Document Type:Article
Language:English
Date of Publication (online):2021/01/04
Year of first Publication:2011
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/04/23
Tag:Highwire; MYCBP2; Neuron; PAM; PHR1; Pain; TRP Channels; Trafficking; Ubiquitin Ligase; p38 MAPK
Volume:286.2011
Issue:5
Page Number:10
First Page:3671
Last Page:3680
Institutes:Medizin
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International