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TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors.

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Gao Yingwei[1] * ; Ma Ruining[1] * ; Weng Weiji[1] * ; Zhang Heng[2] ; Wang Yingping[1] ; Guo Rongjun[1] ; Gu Xiaokun[1] ; Yang Yang[1] ; Yang Fan[2] ; Zhou Aiwu[3] ; Cheng Jinke[1] ; Chen Zhe-Yu[4] ; Zhu Michael X[5] ; Li Yong[1] ;
机构： [1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, and Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [2]Department of Biophysics and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China [3]Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [4]Institute of Brain Science, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China [5]Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
出处：
DOI： 10.1016/j.celrep.2022.110972
ISSN：

摘要：
The molecular mechanism underlying the functional interaction between H1R and TRPV1 remains unclear. We show here that H1R directly binds to the carboxy-terminal region of TRPV1 at residues 715-725 and 736-749. Cell-penetrating peptides containing these sequences suppress histamine-induced scratching behavior in a cheek injection model. The H1R-TRPV1 binding is kept at a minimum at rest in mouse trigeminal neurons due to TRPV1 SUMOylation and it is enhanced upon histamine treatment through a transient TRPV1 deSUMOylation. The knockin of the SUMOylation-deficient TRPV1K823R 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.Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

基金：
This study was supported in part by grants from the National Natural Science Foundation of China (31830031, 82071510, and 31761163002 to Y.L.), the National Key Research and Development Program of China (2020YFA0803602 to Y.L.), and Innovative Research Team of High-Level Local Universities in Shanghai (SHSMU-ZDCX20211102).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
JCR分区：
出版当年[2020]版：
Q1 CELL BIOLOGY
最新[2023]版：
Q1 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, and Faculty of Basic Medicine, Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Gao Yingwei,Ma Ruining,Weng Weiji,et al.TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors.[J].CELL REPORTS.2022,39(11):doi:10.1016/j.celrep.2022.110972.
APA：
Gao Yingwei,Ma Ruining,Weng Weiji,Zhang Heng,Wang Yingping...&Li Yong.(2022).TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors..CELL REPORTS,39,(11)
MLA：
Gao Yingwei,et al."TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors.".CELL REPORTS 39..11(2022)

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