TRPV1 SUMOylation regulates nociceptive signaling in models of inflammatory pain

Yan Wang, Yingwei Gao, Quan Tian, Qi Deng, Yangbo Wang, Tian Zhou, Qiang Liu, Kaidi Mei, Yingping Wang, Huiqing Liu, Ruining Ma, Yuqiang Ding, Weifang Rong, Jinke Cheng, Jing Yao (), Tian-Le Xu, Michael X. Zhu and Yong Li ()
Additional contact information
Yan Wang: Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine
Yingwei Gao: Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine
Quan Tian: Wuhan University
Qi Deng: Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine
Yangbo Wang: Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine
Tian Zhou: Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine
Qiang Liu: Wuhan University
Kaidi Mei: Wuhan University
Yingping Wang: Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine
Huiqing Liu: Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine
Ruining Ma: Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine
Yuqiang Ding: Tongji University School of Medicine
Weifang Rong: Shanghai Jiao Tong University School of Medicine
Jinke Cheng: Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine
Jing Yao: Wuhan University
Tian-Le Xu: Shanghai Jiao Tong University School of Medicine
Michael X. Zhu: The University of Texas Health Science Center at Houston
Yong Li: Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-03974-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03974-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-03974-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().