TY  - JOUR
A1  - Holland, Sabrina Marion
A1  - Coste, Ovidiu
A1  - Zhang, Dong Dong
A1  - Pierre, Sandra C.
A1  - Geisslinger, Gerd
A1  - Scholich, Klaus
T1  - The ubiquitin ligase MYCBP2 regulates transient receptor potential vanilloid receptor 1 (TRPV1) internalization through inhibition of p38 MAPK signaling
T2  - Journal of biological chemistry
N2  - 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.
KW  - Neuron
KW  - p38 MAPK
KW  - Trafficking
KW  - TRP Channels
KW  - Ubiquitin Ligase
KW  - MYCBP2
KW  - PAM
KW  - PHR1
KW  - Highwire
KW  - Pain
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76562
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-765621
SN  - 0021-9258
VL  - 286.2011
IS  - 5
SP  - 3671
EP  - 3680
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -