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Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel

Xiaoyi Mo1, Peiyuan Pang1, Yulin Wang1

  • 1State Key Laboratory of Virology, College of Life Sciences, Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.

Elife
|June 10, 2022
PubMed

Insights

Tyrosine phosphorylation regulates the activity of the TRPV2 ion channel, crucial for immune cell function. This phosphorylation, controlled by JAK1 and PTPN1, impacts macrophage phagocytosis and pain signaling.

Area of Science:

  • Molecular Biology
  • Immunology
  • Neuroscience

Background:

  • Transient receptor potential vanilloid 2 (TRPV2) is a key ion channel involved in various physiological and pathological processes, including immune responses.
  • The precise endogenous signaling pathways governing TRPV2 channel activity remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the endogenous signaling cascades that regulate the gating and sensitivity of TRPV2.
  • To investigate the role of tyrosine phosphorylation in modulating TRPV2 function in macrophages and neurons.

Main Methods:

  • Utilized rat bone marrow-derived macrophages and dorsal root ganglia (DRG) neurons to study endogenous TRPV2.
  • Employed biochemical assays to identify specific tyrosine phosphorylation sites on TRPV2.
  • Investigated the roles of Janus kinase 1 (JAK1) and protein tyrosine phosphatase non-receptor type 1 (PTPN1) in regulating TRPV2 phosphorylation.

Main Results:

  • Enhanced tyrosine phosphorylation significantly altered the chemical and thermal sensitivities of TRPV2.
  • Identified JAK1 as the kinase responsible for phosphorylating TRPV2 at Tyr(335), Tyr(471), and Tyr(525).
  • Demonstrated that JAK1-mediated phosphorylation is essential for maintaining TRPV2 activity and macrophage phagocytosis, and that PTPN1 dynamically balances this phosphorylation.

Conclusions:

  • The phosphorylation/dephosphorylation balance of TRPV2 by JAK1 and PTPN1 establishes its basal chemical and thermal sensitivity.
  • This regulatory mechanism is critical for TRPV2 function in immune cells and neurons.
  • Targeting this TRPV2 phosphorylation pathway offers potential therapeutic strategies for related physiopathological conditions.
Keywords:
TRPV2biochemistrychemical biologymolecular biophysicsnociceptionphagocytosisphosphorylationratstructural biologytemperature gating

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