TRPV1 SUMOylation regulates nociceptive signaling in models of inflammatory pain

被引：48

作者：

Wang, Yan ^{[1
]}

Gao, Yingwei ^{[1
]}

Tian, Quan ^{[2
]}

Deng, Qi ^{[1
]}

Wang, Yangbo ^{[1
]}

Zhou, Tian ^{[1
]}

Liu, Qiang ^{[2
]}

Mei, Kaidi ^{[2
]}

Wang, Yingping ^{[1
]}

Liu, Huiqing ^{[1
]}

Ma, Ruining ^{[1
]}

Ding, Yuqiang ^{[3
]}

Rong, Weifang ^{[4
]}

Cheng, Jinke ^{[1
]}

Yao, Jing ^{[2
]}

Xu, Tian-Le ^{[4
]}

Zhu, Michael X. ^{[5
]}

Li, Yong ^{[1
]}

机构：

[1] Inst Med Sci, Shanghai Key Lab Tumor Microenvironment & Inflamm, Dept Biochem & Mol Cell Biol, Shanghai 200025, Peoples R China

[2] Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Hubei, Peoples R China

[3] Tongji Univ, Sch Med, Dept Anat & Neurobiol, Collaborat Innovat Ctr Brain Sci, Shanghai 200092, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Dept Anat & Physiol, Shanghai 200025, Peoples R China

[5] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国国家自然科学基金; 美国国家卫生研究院; 中国博士后科学基金;

关键词：

PROTEIN-KINASE-C; VANILLOID RECEPTOR TRPV1; RAT HIPPOCAMPAL-NEURONS; PRIMARY SENSORY NEURONS; ACTIVATED ION-CHANNEL; CAPSAICIN RECEPTOR; DIRECT PHOSPHORYLATION; POTENTIAL VANILLOID-1; THERMAL HYPERALGESIA; HEAT HYPERALGESIA;

D O I：

10.1038/s41467-018-03974-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Although TRPV1 channels represent a key player of noxious heat sensation, the precise mechanisms for thermal hyperalgesia remain unknown. We report here that conditional knockout of deSUMOylation enzyme, SENP1, in mouse dorsal root ganglion (DRG) neurons exacerbated thermal hyperalgesia in both carrageenan- and Complete Freund's adjuvant-induced inflammation models. TRPV1 is SUMOylated at a C-terminal Lys residue (K822), which specifically enhances the channel sensitivity to stimulation by heat, but not capsaicin, protons or voltage. TRPV1 SUMOylation is decreased by SENP1 but upregulated upon peripheral inflammation. More importantly, the reduced ability of TRPV1 knockout mice to develop inflammatory thermal hyperalgesia was rescued by viral infection of lumbar 3/4 DRG neurons of wild-type TRPV1, but not its SUMOylation-deficient mutant, K822R. These data suggest that TRPV1 SUMOylation is essential for the development of inflammatory thermal hyperalgesia, through a mechanism that involves sensitization of the channel response specifically to thermal stimulation.

引用

页数：17

共 75 条

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