Cargando…

Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel

Transient receptor potential vanilloid 2 (TRPV2) is a multimodal ion channel implicated in diverse physiopathological processes. Its important involvement in immune responses has been suggested such as in the macrophages’ phagocytosis process. However, the endogenous signaling cascades controlling t...

Descripción completa

Detalles Bibliográficos
Autores principales: Mo, Xiaoyi, Pang, Peiyuan, Wang, Yulin, Jiang, Dexiang, Zhang, Mengyu, Li, Yang, Wang, Peiyu, Geng, Qizhi, Xie, Chang, Du, Hai-Ning, Zhong, Bo, Li, Dongdong, Yao, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282855/
https://www.ncbi.nlm.nih.gov/pubmed/35686730
http://dx.doi.org/10.7554/eLife.78301
_version_ 1784747202420146176
author Mo, Xiaoyi
Pang, Peiyuan
Wang, Yulin
Jiang, Dexiang
Zhang, Mengyu
Li, Yang
Wang, Peiyu
Geng, Qizhi
Xie, Chang
Du, Hai-Ning
Zhong, Bo
Li, Dongdong
Yao, Jing
author_facet Mo, Xiaoyi
Pang, Peiyuan
Wang, Yulin
Jiang, Dexiang
Zhang, Mengyu
Li, Yang
Wang, Peiyu
Geng, Qizhi
Xie, Chang
Du, Hai-Ning
Zhong, Bo
Li, Dongdong
Yao, Jing
author_sort Mo, Xiaoyi
collection PubMed
description Transient receptor potential vanilloid 2 (TRPV2) is a multimodal ion channel implicated in diverse physiopathological processes. Its important involvement in immune responses has been suggested such as in the macrophages’ phagocytosis process. However, the endogenous signaling cascades controlling the gating of TRPV2 remain to be understood. Here, we report that enhancing tyrosine phosphorylation remarkably alters the chemical and thermal sensitivities of TRPV2 endogenously expressed in rat bone marrow-derived macrophages and dorsal root ganglia (DRG) neurons. We identify that the protein tyrosine kinase JAK1 mediates TRPV2 phosphorylation at the molecular sites Tyr(335), Tyr(471), and Tyr(525). JAK1 phosphorylation is required for maintaining TRPV2 activity and the phagocytic ability of macrophages. We further show that TRPV2 phosphorylation is dynamically balanced by protein tyrosine phosphatase non-receptor type 1 (PTPN1). PTPN1 inhibition increases TRPV2 phosphorylation, further reducing the activation temperature threshold. Our data thus unveil an intrinsic mechanism where the phosphorylation/dephosphorylation dynamic balance sets the basal chemical and thermal sensitivity of TRPV2. Targeting this pathway will aid therapeutic interventions in physiopathological contexts.
format Online
Article
Text
id pubmed-9282855
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-92828552022-07-15 Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel Mo, Xiaoyi Pang, Peiyuan Wang, Yulin Jiang, Dexiang Zhang, Mengyu Li, Yang Wang, Peiyu Geng, Qizhi Xie, Chang Du, Hai-Ning Zhong, Bo Li, Dongdong Yao, Jing eLife Biochemistry and Chemical Biology Transient receptor potential vanilloid 2 (TRPV2) is a multimodal ion channel implicated in diverse physiopathological processes. Its important involvement in immune responses has been suggested such as in the macrophages’ phagocytosis process. However, the endogenous signaling cascades controlling the gating of TRPV2 remain to be understood. Here, we report that enhancing tyrosine phosphorylation remarkably alters the chemical and thermal sensitivities of TRPV2 endogenously expressed in rat bone marrow-derived macrophages and dorsal root ganglia (DRG) neurons. We identify that the protein tyrosine kinase JAK1 mediates TRPV2 phosphorylation at the molecular sites Tyr(335), Tyr(471), and Tyr(525). JAK1 phosphorylation is required for maintaining TRPV2 activity and the phagocytic ability of macrophages. We further show that TRPV2 phosphorylation is dynamically balanced by protein tyrosine phosphatase non-receptor type 1 (PTPN1). PTPN1 inhibition increases TRPV2 phosphorylation, further reducing the activation temperature threshold. Our data thus unveil an intrinsic mechanism where the phosphorylation/dephosphorylation dynamic balance sets the basal chemical and thermal sensitivity of TRPV2. Targeting this pathway will aid therapeutic interventions in physiopathological contexts. eLife Sciences Publications, Ltd 2022-06-10 /pmc/articles/PMC9282855/ /pubmed/35686730 http://dx.doi.org/10.7554/eLife.78301 Text en © 2022, Mo, Pang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Mo, Xiaoyi
Pang, Peiyuan
Wang, Yulin
Jiang, Dexiang
Zhang, Mengyu
Li, Yang
Wang, Peiyu
Geng, Qizhi
Xie, Chang
Du, Hai-Ning
Zhong, Bo
Li, Dongdong
Yao, Jing
Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
title Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
title_full Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
title_fullStr Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
title_full_unstemmed Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
title_short Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
title_sort tyrosine phosphorylation tunes chemical and thermal sensitivity of trpv2 ion channel
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282855/
https://www.ncbi.nlm.nih.gov/pubmed/35686730
http://dx.doi.org/10.7554/eLife.78301
work_keys_str_mv AT moxiaoyi tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT pangpeiyuan tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT wangyulin tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT jiangdexiang tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT zhangmengyu tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT liyang tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT wangpeiyu tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT gengqizhi tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT xiechang tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT duhaining tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT zhongbo tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT lidongdong tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel
AT yaojing tyrosinephosphorylationtuneschemicalandthermalsensitivityoftrpv2ionchannel