TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors
Yingwei Gao, Ruining Ma, Weiji Weng, Heng Zhang, Yingping Wang, Rongjun Guo, Xiaokun Gu, Yang Yang, Fan Yang, Aiwu Zhou, Jinke Cheng, Zhe-Yu Chen, Michael X. Zhu, Yong Li
Abstract
mutant in mice leads to constitutive enhancement of H1R-TRPV1 binding, which exacerbates scratching behaviors induced by histamine. Conversely, SENP1 conditional knockout in sensory neurons enhances TRPV1 SUMOylation and suppresses the histamine-induced scratching response. In addition to interfering with binding, TRPV1 SUMOylation promotes H1R degradation through ubiquitination. Our work unveils the molecular mechanism of histaminergic itch by which H1R directly binds to deSUMOylated TRPV1 to facilitate the transduction of the pruritogen signal to the scratching response.
Topics & Concepts
TRPV1SUMO proteinReceptorCell biologyChemistryEndosomeBiologyBiochemistryTransient receptor potential channelGeneUbiquitinIon Channels and ReceptorsDermatology and Skin DiseasesHerbal Medicine Research Studies