Palmitoylation by ZDHHC4 inhibits TRPV1-mediated nociception

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.

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Publication Details

Journal
EMBO Reports
Published
2024-11-11
DOI
https://doi.org/10.1038/s44319-024-00317-0
Citations
5
Primary Topic
Ion Channels and Receptors
Type
article
Field-Weighted Citation Impact
1.81

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article

Palmitoylation by ZDHHC4 inhibits TRPV1-mediated nociception

Cheng Tang, Junyan Hu, Youjing Zhang, Xu-Feng Cheng et al.
5 citations
EMBO Reports
Ion Channels and Receptors
1.81
article

Palmitoylation by ZDHHC4 inhibits TRPV1-mediated nociception

Cheng Tang, Junyan Hu, Youjing Zhang, Xu-Feng Cheng, Jing Yao, Dongdong Li, Li Yang, Zefeng Chen, Yin Yuan, Chang Xie, Mengyu Zhang
article en
5 citations

Abstract

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.

EMBO ReportsVol. 26(1)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Hunan Normal University (CN), Université Paris-Seine (FR), Wuhan University (CN), Sorbonne Université (FR), Institut de Biologie Paris-Seine (FR), Wuchang University of Technology (CN), Neurosciences Paris-Seine (FR), Hubei University (CN)
National Natural Science Foundation of China, Wuhan University, National Key Research and Development Program of China
Good health and well-being
Openalex Percentile: Top 16%
Ion Channels and Receptors
1.81
DOIOpen Access PDFOpenAlex
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