Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel

  1. Xiaoyi Mo
  2. Peiyuan Pang
  3. Yulin Wang
  4. Dexiang Jiang
  5. Mengyu Zhang
  6. Yang Li
  7. Peiyu Wang
  8. Qizhi Geng
  9. Chang Xie
  10. Hai-Ning Du
  11. Bo Zhong
  12. Dongdong Li
  13. Jing Yao  Is a corresponding author
  1. Wuhan University, China
  2. 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.

The following data sets were generated

Article and author information

Author details

  1. Xiaoyi Mo

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Peiyuan Pang

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yulin Wang

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Dexiang Jiang

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Mengyu Zhang

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Yang Li

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Peiyu Wang

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Qizhi Geng

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Chang Xie

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Hai-Ning Du

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Bo Zhong

    Department of Anesthesiology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Dongdong Li

    Neuroscience Paris Seine, CNRS, INSERM, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6731-4771
  13. Jing Yao

    Department of Anesthesiology, Wuhan University, Wuhan, China
    For correspondence
    jyao@whu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1844-3988

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

  1. Andrés Jara-Oseguera, The University of Texas at Austin, United States

Publication history

  1. Received: March 1, 2022
  2. Accepted: June 9, 2022
  3. Accepted Manuscript published: June 10, 2022 (version 1)

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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  1. Xiaoyi Mo
  2. Peiyuan Pang
  3. Yulin Wang
  4. Dexiang Jiang
  5. Mengyu Zhang
  6. Yang Li
  7. Peiyu Wang
  8. Qizhi Geng
  9. Chang Xie
  10. Hai-Ning Du
  11. Bo Zhong
  12. Dongdong Li
  13. Jing Yao
(2022)
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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