State 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
State 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
Yulin Wang
State 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
Dexiang Jiang
State 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
Mengyu Zhang
State 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
Yang Li
State 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
Peiyu Wang
State 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
Qizhi Geng
State 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
Chang Xie
State 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
Hai-Ning Du
State 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
Bo Zhong
State 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
State 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; The Key Laboratory of Neural and Vascular Biology, Ministry of Education Hebei Medical University, Shijiazhuang, China
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.
