Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
- Wuhan University, China
- CNRS, INSERM, Sorbonne Université, France
Abstract
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. 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.
Data availability
All major datasets supporting the conclusions of this article has been deposited at Dryad, https://doi.org/10.5061/dryad.41ns1rng6.
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Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channelDryad Digital Repository, doi:10.5061/dryad.41ns1rng6.
Article and author information
Author details
Funding
National Natural Science Foundation of China (32171147)
- Jing Yao
National Natural Science Foundation of China (31830031)
- Jing Yao
National Natural Science Foundation of China (31929003)
- Jing Yao
National Natural Science Foundation of China (31871174)
- Jing Yao
National Natural Science Foundation of China (31671209)
- Jing Yao
Fundamental Research Funds for the Central Universities (2042021KF0218)
- Jing Yao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animals were housed in the specific pathogen-free animal facility at Wuhan University and all animal experiments were following protocols approved by the Institutional Animal Care and Use Committee of Wuhan University (NO. WDSKY0201804) and adhered to the Chinese National Laboratory Animal-Guideline for Ethical Review of Animal Welfare. The animals were euthanatized with CO2 followed by various studies.
Reviewing Editor
- Andrés Jara-Oseguera, The University of Texas at Austin, United States
Version history
- Received: March 1, 2022
- Preprint posted: March 5, 2022 (view preprint)
- Accepted: June 9, 2022
- Accepted Manuscript published: June 10, 2022 (version 1)
- Version of Record published: July 14, 2022 (version 2)
Copyright
© 2022, Mo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
eLife 11:e78301.
https://doi.org/10.7554/eLife.78301
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