Palmitoylation by ZDHHC4 inhibits TRPV1-mediated nociception.

Autor:	Zhang Y; State Key Laboratory of Virology, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, Hubei, 430072, China., Zhang M; State Key Laboratory of Virology, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, Hubei, 430072, China., Tang C; The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, China., Hu J; State Key Laboratory of Virology, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, Hubei, 430072, China., Cheng X; State Key Laboratory of Virology, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, Hubei, 430072, China., Li Y; State Key Laboratory of Virology, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, Hubei, 430072, China., Chen Z; State Key Laboratory of Virology, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, Hubei, 430072, China., Yin Y; The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, China., Xie C; State Key Laboratory of Virology, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, Hubei, 430072, China., Li D; Sorbonne Université - CNRS - INSERM, Institut de Biologie Paris Seine, Neuroscience Paris Seine, Paris, 75005, France. dongdong.li@inserm.fr., Yao J; State Key Laboratory of Virology, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, Hubei, 430072, China. jyao@whu.edu.cn.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Nov 11. Date of Electronic Publication: 2024 Nov 11.
DOI:	10.1038/s44319-024-00317-0
Abstrakt:	Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin-sensitive ion channel implicated in pain sensation. While TRPV1 potentiation in hyperalgesia development has been extensively investigated, its functional decline during pain relief remains largely unexplored. Here, by molecular, electrophysiological and in vivo evidence, we reveal that S-palmitoylation fine-tunes TRPV1 function by promoting its degradation via the lysosome pathway thereby facilitating inflammatory pain relief. The palmitoyl acyltransferase ZDHHC4 is identified to physically interact with TRPV1 and to catalyze S-palmitoylation at the cysteine residues C157, C362, C390, and C715 of the channel. Furthermore, we show that TRPV1 palmitoylation is counterbalanced by the depalmitoylase acyl-protein thioesterase 1 (APT1), thereby reinstating pain sensation. These findings provide important mechanistic insights into the relief phase of inflammatory pain. Competing Interests: Disclosure and competing interests statement The authors declare no competing interests. (© 2024. The Author(s).)
Databáze:	MEDLINE
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