Affinage

TRPV2

Transient receptor potential cation channel subfamily V member 2 · UniProt Q9Y5S1

Length
764 aa
Mass
86.0 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRPV2 is a Ca2+-permeable, non-selective cation channel that functions as a polymodal sensor of heat, mechanical/osmotic stress, lipids, and small-molecule agonists, transducing these stimuli into Ca2+ signals that drive cytoskeletal remodeling, secretion, and gene expression across diverse non-neuronal cell types (PMID:29728656, PMID:18984736, PMID:36744297). Structurally it is a homotetramer with an upper (selectivity filter) and lower (S6) gate, in which agonist (resiniferatoxin) binding drives a two-fold symmetric opening of the selectivity filter wide enough to permeate large organic cations, while rotation of the ankyrin-repeat domain couples through the TRP domain to S6 to open the pore (PMID:26779611, PMID:29728656, PMID:31090543). Distinct ligand sites govern gating: cannabidiol binds a hydrophobic pocket between S5 and S6 of adjacent subunits acting through the S4-S5 linker, 2-APB binds a TRPV2-specific S5/S4-S5 interface site (His521/Arg539), and an endogenous cholesterol molecule occupies the vanilloid binding pocket as an inhibitor that is relieved by methyl-β-cyclodextrin or estradiol (PMID:31566564, PMID:35484159, PMID:36163384). Channel activity is tuned post-translationally by Ca2+-dependent desensitization via PIP2 hydrolysis (PMID:20926660), methionine oxidation at M528/M607 (heat-sensitizing and required for macrophage phagocytosis) (PMID:31719194), and JAK1-mediated tyrosine phosphorylation at Tyr335/471/525 balanced by the phosphatase PTPN1 (PMID:35686730). A central regulatory theme is stimulus-triggered translocation from intracellular pools to the plasma membrane, driven by insulin/PI3K, growth factors, lysophospholipids, adrenomedullin, mechanical stress, and cAMP, which controls Ca2+ entry in beta-cell insulin secretion, cancer cell migration, and cardiac mechanosensation (PMID:18984736, PMID:19321128, PMID:25677550, PMID:23786999). Through this gating and trafficking, TRPV2 engages downstream Ca2+-calcineurin-NFAT signaling in osteoclastogenesis and brown adipocyte regulation (PMID:20980052, PMID:27318696), calpain/talin and RhoA/Rac1 cascades governing leading-edge dynamics and invasion (PMID:36744297, PMID:30851707), IGF-1/PI3K/Akt signaling sustaining cardiac structure and function (PMID:24874017, PMID:23786999), and a cytoplasmic cGAS/STING-derepressed Ca2+ release pathway that activates CaMKK2/AMPK to protect replication forks (PMID:36696898).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2003 Low

    Established the basic biochemical and localization properties of TRPV2, addressing whether the channel is processed and where it resides in cells.

    Evidence RT-PCR, N-glycosylation deglycosylation assays, and immunofluorescence in F-11 cells

    PMID:14622291

    Open questions at the time
    • Single lab, indirect localization readout
    • Overexpression artifact possible for plasma membrane signal
    • No functional channel measurement
  2. 2008 High

    Showed that stimulus-driven plasma membrane translocation, not just intrinsic gating, controls TRPV2 function, answering how an intracellular channel becomes active for physiological Ca2+ entry.

    Evidence GFP-TRPV2 imaging, surface detection, Ca2+ imaging, shRNA knockdown, and insulin receptor knockout in beta-cells (also #17, #19, #20, #21)

    PMID:18984736 PMID:19321128 PMID:20854263 PMID:23741410 PMID:25677550

    Open questions at the time
    • Molecular machinery of vesicular trafficking not defined
    • Translocation vs. direct activity contributions not always separated
    • PI3K can promote activity independent of trafficking (#18), unresolved
  3. 2010 High

    Resolved the mechanism of Ca2+-dependent desensitization, distinguishing PIP2 hydrolysis from calmodulin as the negative regulator of the channel.

    Evidence Whole-cell patch-clamp with simultaneous confocal PIP2 probe imaging and calmodulin perturbation

    PMID:20926660

    Open questions at the time
    • Calmodulin still binds the C-terminus (#12) with unclear functional role
    • Structural basis of PIP2 action not resolved
    • Lipid binding site not mapped in this study
  4. 2016 High

    Provided the first atomic-scale gating model by showing ankyrin-repeat domain rotation coupled through the TRP domain to S6, and defined two-gate architecture.

    Evidence Cryo-EM of rabbit and full-length TRPV2 (also #1)

    PMID:26779611 PMID:27021073

    Open questions at the time
    • Resolution limited (~4-5 Å)
    • Ligand-bound and physiological lipid states not yet captured
    • Coupling of upper and lower gates incompletely defined
  5. 2018 High

    Defined the structural basis for dual Ca2+ and large organic cation permeation by showing agonist-induced two-fold symmetric selectivity filter opening, an intrinsic gating property.

    Evidence X-ray crystallography and cryo-EM with electrophysiology in Ca2+/RTx-bound states (also #4, #5)

    PMID:29728656 PMID:30598551 PMID:31090543

    Open questions at the time
    • Physiological trigger of symmetry transition in vivo unclear
    • Pore turret role beyond functional importance not mechanistically dissected
    • Heat-induced conformations not captured
  6. 2019 High

    Mapped distinct small-molecule and lipid binding sites (CBD between S5/S6; later 2-APB at an S5/S4-S5 interface) and an endogenous cholesterol inhibitor in the vanilloid pocket, explaining polypharmacology and endogenous tone.

    Evidence Cryo-EM in nanodiscs with mutagenesis and electrophysiology (also #6, #7, #8)

    PMID:31566564 PMID:35484159 PMID:36163384 PMID:37199723

    Open questions at the time
    • Endogenous heat-sensing site distinct from agonist sites (#38) not structurally resolved
    • Physiological regulation of cholesterol occupancy unknown
    • How CBD sensitization to 2-APB but not heat is encoded structurally not fully explained
  7. 2019 High

    Identified covalent activating modifications, establishing TRPV2 as an oxidation- and phosphorylation-gated channel with defined writers, erasers, and residues.

    Evidence Excised-patch electrophysiology, mutagenesis, mass spectrometry, and kinase/phosphatase assays (also #11)

    PMID:31719194 PMID:35686730

    Open questions at the time
    • Physiological sources of oxidation in vivo not fully defined
    • Crosstalk between oxidation, phosphorylation, and lipid regulation unmapped
    • Structural consequences of modifications not visualized
  8. 2014 High

    Established TRPV2 as a cardiac mechanosensor required for structural integrity and Ca2+ handling, linking it to IGF-1/PI3K/Akt signaling and disease.

    Evidence Conditional cardiac KO with echocardiography, Ca2+ handling, stretch experiments, and IGF-1 rescue (also #23, #24)

    PMID:23786999 PMID:24874017 PMID:25616416

    Open questions at the time
    • Direct stretch-sensing mechanism at molecular level not resolved
    • Relationship between sarcolemmal accumulation and pathology vs. protection context-dependent
    • No timeline evidence of a human Mendelian mutation
  9. 2018 Medium

    Connected TRPV2-mediated Ca2+ entry to effector pathways driving cell migration, invasion, and cytoskeletal remodeling in cancer and immune contexts.

    Evidence Silencing/pharmacology with calpain/talin, RhoA/Rac1, and ERK readouts and in vivo invasion models (also #34, #36, #37)

    PMID:20093382 PMID:26993604 PMID:30851707 PMID:36744297

    Open questions at the time
    • Largely single-lab studies per cell type
    • Direct vs. indirect coupling to calpain/RhoA not fully established
    • Context-dependent pro- vs. anti-invasive effects unresolved
  10. 2018 Medium

    Demonstrated TRPV2's role in innate and adaptive immune cell function, including phagocytosis, viral penetration, and B cell synapse formation, via Ca2+ and membrane mechanics.

    Evidence siRNA/conditional KO, lipid raft fractionation, reconstitution with Ca2+-impermeable mutants, and functional immune assays (also #31, #33)

    PMID:29523858 PMID:36261399 PMID:38353705

    Open questions at the time
    • Recruitment mechanism to phagocytic cup/synapse not fully defined
    • LRMDA axis mechanistic detail incomplete
    • Single-lab findings per immune cell type
  11. 2023 Medium

    Placed TRPV2 in a genome-stability pathway, showing STING dissociation derepresses TRPV2 to release ER Ca2+ and protect replication forks via CaMKK2/AMPK.

    Evidence STING-TRPV2 co-immunoprecipitation, Ca2+ measurements, and pathway epistasis

    PMID:36696898

    Open questions at the time
    • Single Co-IP for STING-TRPV2 interaction without structural validation
    • ER-resident vs. plasma membrane pool contribution not separated
    • Generality across cell types untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the structurally defined heat-sensing pathway, distinct agonist/lipid sites, and post-translational modifications integrate with stimulus-gated trafficking to set cell-type-specific TRPV2 output remains unresolved.
  • No structure of a heat-activated state
  • Trafficking machinery and recruitment signals undefined
  • Integration of oxidation, phosphorylation, lipid, and PIP2 inputs not unified mechanistically

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0140299 molecular sensor activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-397014 Muscle contraction 3
Partners
ACBD3CALM1JAK1LRMDAPRKACAPTPN1STING1TRPV1

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 Cryo-EM structure of rabbit TRPV2 at ~4 Å resolution reveals that S6 adopts a conformation distinct from TRPV1, and that rotation of the ankyrin-repeat domain is coupled to pore opening via the TRP domain; rearrangements in S6 secondary structure modulate pore opening. Cryo-electron microscopy (cryo-EM) structural determination at ~4 Å resolution Nature structural & molecular biology High 26779611
2016 Full-length TRPV2 cryo-EM structure at ~5 Å shows two constrictions (upper and lower gates), with wider upper and lower gates compared to closed and agonist-activated TRPV1, suggesting structural diversity among TRPV channels contributes to functional divergence. Cryo-electron microscopy (cryo-EM) of full-length TRPV2 Nature communications High 27021073
2019 CBD binds TRPV2 through a hydrophobic pocket between S5 and S6 helices of adjacent subunits, a site distinct from known ligand/lipid sites in other TRP channels; the S4-S5 linker plays a critical role in channel gating upon CBD binding. Two distinct TRPV2 apo states were visualized in a lipid environment. Cryo-EM of full-length rat TRPV2 in nanodiscs in apo and CBD-bound states eLife High 31566564
2018 Crystal structures of rabbit TRPV2 in Ca2+-bound and resiniferatoxin (RTx)+Ca2+-bound forms reveal that RTx binding leads to two-fold symmetric opening of the selectivity filter wide enough for large organic cation permeation, establishing a structural basis for dual Ca2+ and large organic cation permeation. X-ray crystallography at 3.9 Å (Ca2+-bound) and 3.1 Å (RTx+Ca2+-bound) with functional electrophysiological characterization Nature structural & molecular biology High 29728656
2018 Cryo-EM structures of rat TRPV2 reveal fully open and partially open states and resolve the full-length pore turret; activity assays demonstrate the pore turret is important for channel function, and structural data suggest lipid binding at the vanilloid pocket can regulate the lower gate and couple to the upper gate through a pore-turret-facilitated mechanism. Cryo-EM at 4.0 Å and 3.6 Å resolution combined with channel activity assays Nature structural & molecular biology High 30598551
2019 RTx induces two-fold symmetric conformations of TRPV2 in both nanodisc and amphipol environments (more pronounced in nanodiscs), establishing that symmetry transitions during gating are an intrinsic property of TRPV2 and not solely due to crystal packing. Cryo-EM of full-length rabbit TRPV2 in complex with RTx in nanodiscs and amphipol eLife High 31090543
2022 Cryo-EM structures of rat TRPV2 in lipid nanodiscs activated by 2-APB identify a TRPV2-specific binding site at the interface of S5 of one monomer and the S4-S5 linker of the adjacent monomer; His521 and Rac539 are key residues for 2-APB activation confirmed by mutagenesis and electrophysiology. Simultaneous binding of 2-APB and CBD was demonstrated structurally. Cryo-EM in lipid nanodiscs, in silico docking, electrophysiological studies, mutagenesis Nature communications High 35484159
2022 Cryo-EM structures at 2.8–3.3 Å reveal an endogenous cholesterol molecule inside the vanilloid binding pocket (VBP) of TRPV2 with 'head down, tail up' configuration that antagonizes ligand activation; methyl-β-cyclodextrin removes cholesterol from VBP; estradiol potentiates 2-APB activation by disturbing cholesterol binding; 2-APB binds within the VBP. Cryo-EM at 2.8–3.3 Å resolution; pharmacological assays Nature chemical biology High 36163384
2023 CBD sensitizes TRPV2 current responses to 2-APB by over two orders of magnitude without sensitizing to heat; cryo-EM reveals a new small-molecule binding site in the pore domain in addition to the previously reported CBD site. Strong sensitization by CBD is specific to TRPV2 (and TRPV3) and not transferred to TRPV1 by mutations at the CBD binding site or pore domain. Patch-clamp electrophysiology, cryo-EM, mutagenesis eLife High 37199723
2010 TRPV2 Ca2+-dependent desensitization is mediated by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), not calmodulin; simultaneous confocal imaging and electrophysiology showed TRPV2 desensitization was concomitant with PIP2 depletion. Calmodulin inhibitors and mutant calmodulin did not alter desensitization. Whole-cell patch-clamp, simultaneous confocal imaging with fluorescent PIP2-binding probe, calmodulin inhibitors, mutant calmodulin co-expression The Journal of neuroscience High 20926660
2019 Oxidation of methionine residues M528 and M607 activates and sensitizes TRPV2 to heat; chloramine-T, UVA light, and ROS-producing photosensitizers activate TRPV2 in excised inside-out patches (direct channel effect); DTT plus methionine sulfoxide reductase partially reverses activation; mass spectrometry confirms oxidation of these residues; macrophage phagocytosis is reduced by TRPV2 inhibitor or DTT. Electrophysiology (whole-cell and excised inside-out patches), site-directed mutagenesis (M528I, M607I), mass spectrometry on purified TRPV2 protein, pharmacological assays in macrophages Proceedings of the National Academy of Sciences of the United States of America High 31719194
2022 JAK1 mediates TRPV2 tyrosine phosphorylation at Tyr335, Tyr471, and Tyr525; enhanced tyrosine phosphorylation alters chemical and thermal sensitivity of TRPV2 in macrophages and DRG neurons; PTPN1 dephosphorylates TRPV2, dynamically balancing its activity; JAK1 phosphorylation is required for TRPV2 activity and macrophage phagocytic ability. Electrophysiology, site-directed mutagenesis, kinase/phosphatase assays, phagocytosis assays in macrophages and DRG neurons eLife High 35686730
2010 Calmodulin binds to the C-terminus of TRPV2 (residues 654–683) via a 1-5-10 consensus motif; R679A and K681A mutations reduce binding affinity by 50%, and double mutation K661A/K664A reduces affinity by 75%, identifying basic residues critical for calmodulin interaction. In vitro calmodulin binding assays with peptides, site-directed mutagenesis Amino acids Medium 20686800
2005 TRPV1 and TRPV2 form heteromeric complexes, as demonstrated by co-immunoprecipitation from HEK cells, F-11 cells, and rat DRG lysates; a small population of native DRG neurons co-expresses both channels at the cell surface. Co-immunoprecipitation from transfected mammalian cells and native rat DRG; immunofluorescence co-localization Neuroreport Medium 16237318
2004 TRPV2 forms a complex with PKA and the A-kinase adapter protein ACBD3 in mast cells; TRPV2 is surface-localized and functionally coupled to Ca2+ fluxes and degranulation; cAMP/PKA-dependent regulated phosphorylation is proposed as a modulation mechanism for TRPV2. Co-immunoprecipitation, calcium flux assays, degranulation assays, surface localization by immunostaining in mast cells The Journal of experimental medicine Medium 15249591
2005 RGA protein forms a physiological complex with TRPV2 in mast cells; overexpression of RGA potentiates basal surface localization of TRPV2; elevations in cytosolic cAMP drive plasma membrane localization of TRPV2 in mast cells. Co-immunoprecipitation with polyclonal anti-RGA antibody, flow cytometry for surface TRPV2 quantification, overexpression studies Journal of cellular biochemistry Medium 15547947
2008 In pancreatic beta-cells, insulin induces translocation of TRPV2 from cytoplasm to the plasma membrane via the insulin receptor/PI3K pathway; this translocation increases Ca2+ entry and is required for autocrine insulin secretion stimulated by glucose; knockdown of TRPV2 or insulin receptor attenuates these effects. GFP-TRPV2 live-cell imaging, Myc-tagged TRPV2 surface detection, fura-2 Ca2+ imaging, shRNA knockdown, insulin receptor knockout beta-cells Diabetes High 18984736
2010 Insulin/PI3K signaling accelerates glucose-induced first-phase insulin secretion by recruiting TRPV2 to the plasma membrane in beta-cells; PI3K inhibition abolishes insulin-induced rapid exocytotic response; TRPV2 inhibition (tranilast) or shRNA suppresses first-phase but not second-phase insulin secretion. Total internal reflection fluorescent microscopy (TIRFM) for exocytosis, Ca2+ imaging, PI3K inhibition, tranilast pharmacology, shRNA knockdown The Biochemical journal High 20854263
2006 PI3K promotes TRPV2 channel activity independently of channel translocation to the plasma membrane; cytotoxicity (a read-out of channel activity) is prevented by a pore-domain charge substitution or reduced extracellular Ca2+; PI3K inhibition decreases TRPV2 activity without affecting plasma membrane trafficking. Cytotoxicity assays, stable transfection electrophysiology, direct measurement of cell surface TRPV2 expression, pore-domain mutagenesis Cell calcium Medium 16533525
2009 Lysophospholipids (LPC and LPI) activate TRPV2 via Gq/Go-protein and PI3,4-kinase signaling, causing TRPV2 translocation to the plasma membrane, Ca2+ influx, and increased prostate cancer cell migration; activation depends on lysophospholipid side-chain length and head-group nature. Ca2+ imaging, TRPV2 translocation assays, migration assays, pharmacological signaling pathway dissection in PC3 cells Biochimica et biophysica acta Medium 19321128
2013 Adrenomedullin induces prostate and urothelial cancer cell migration and invasion through TRPV2 translocation to the plasma membrane and subsequent increase in resting calcium levels. TRPV2 translocation assays, Ca2+ imaging, migration and invasion assays in cancer cell lines PloS one Medium 23741410
2015 Focal mechanical stress applied to HT1080 cells causes TRPV2 translocation to the site of stress in a PI3K/Rac1-dependent manner and increases sub-plasma membrane Ca2+ concentration; this Ca2+ elevation requires extracellular Ca2+ and TRPV2, as demonstrated by ruthenium red inhibition and TRPV2 knockdown. Live GFP-TRPV2 and RFP-Akt imaging, mechanical stress application by glass pipette, ruthenium red pharmacology, TRPV2 siRNA knockdown, dominant-negative Rac Physiological reports Medium 25677550
2014 TRPV2 is critical for maintenance of cardiac structure and function; conditional cardiac-specific elimination of TRPV2 causes disorganization of intercalated discs, myocardial conduction defects, impaired Ca2+ handling, and reduced IGF-1 secretion in response to stretch; IGF-1 receptor/PI3K/Akt signaling is significantly downregulated in TRPV2-deficient hearts; IGF-1 administration partially rescues cardiomyopathy. Conditional TRPV2 knockout in adult mice, echocardiography, single cardiomyocyte Ca2+ handling, neonatal cardiomyocyte stretch experiments, Western blotting, IGF-1 rescue experiments Nature communications High 24874017
2013 Sarcolemmal accumulation of TRPV2 is elevated in dilated cardiomyopathy (DCM) patients and three animal models; overexpression of TRPV2 N-terminal domain blocks plasma membrane accumulation and Ca2+ influx, reduces CaMKII phosphorylation and ROS production, prevents ventricular dilation and fibrosis, and improves survival; TRPV2 inhibitor tranilast suppresses DCM progression. Immunological analyses, transgenic/adenoviral N-terminal domain overexpression in DCM animals, Western blotting, echocardiography, survival analysis, tranilast pharmacology Cardiovascular research High 23786999
2015 In dystrophic (mdx) cardiomyocytes, TRPV2 is overexpressed and translocated from intracellular compartments to the sarcolemma and T-tubules; pharmacological inhibition, pore-blocking antibodies, and siRNA ablation of TRPV2 protect mdx cells from stretch-induced abnormal Ca2+ signals, establishing TRPV2 as a stretch-activated Ca2+ influx channel in dystrophic cardiomyopathy. Western blotting, immunocytochemistry, biotinylation assays, patch-clamp pharmacology, confocal Ca2+ imaging, pore-blocking antibodies, siRNA knockdown Cardiovascular research High 25616416
2016 TRPV2 knockout mice have reduced thermogenic gene expression in brown adipose tissue in response to β-adrenergic receptor stimulation, increased body weight and fat, and cold intolerance, indicating TRPV2 plays a role in BAT thermogenesis; Ca2+ influx via TRPV2 is required for thermogenic gene induction. TRPV2 KO mice, gene expression analysis, β-adrenergic stimulation experiments, intracellular Ca2+ manipulation EMBO reports Medium 26882545
2010 TRPV2 activation inhibits spontaneous intestinal circular muscle contraction through nitric oxide (NO) production; mechanical stimuli activate TRPV2-like inward currents in myenteric neurons (inhibited by tranilast); TRPV2 agonists increase intestinal NO production and accelerate gastrointestinal transit in vivo. Dissociated myenteric neuron patch-clamp, isolated intestine contraction assays, NO synthase pathway inhibitors, Ca2+ imaging, in vivo gastrointestinal transit assay The Journal of neuroscience Medium 21147993
2016 TRPV2 contributes to stretch-activated cation currents and myogenic constriction in retinal arterioles; hypoosmotic stretch-induced Ca2+ influx in retinal VSMCs is blocked by tranilast and TRPV2 pore-blocking antibodies; preincubation with TRPV2 blocking antibodies prevents development of myogenic tone. Patch-clamp electrophysiology, Fura-2 Ca2+ microfluorimetry, pressure myography, TRPV2 pore-blocking antibodies, tranilast pharmacology Investigative ophthalmology & visual science Medium 27784066
2010 RANKL upregulates TRPV2 expression in preosteoclasts and drives spontaneous Ca2+ oscillations and transient inward cation currents; TRPV2 silencing reduces Ca2+ oscillation frequency and current amplitude, decreases NFATc1 expression and nuclear translocation, and inhibits osteoclastogenesis. DNA microarray, siRNA silencing of TRPV2, Ca2+ imaging, patch-clamp, Western blotting for NFATc1 Cell calcium Medium 20980052
2018 TRPV2 in Ca2+-calcineurin-NFAT signaling regulates RANKL-dependent osteoclastic differentiation in multiple myeloma; TRPV2 gates Ca2+ influx in MM cells in high Ca2+ environment; SKF96365 inhibition of TRPV2 attenuates osteoclast formation in vitro. Fluo-4 Ca2+ staining, Western blotting, ChIP assays, ELISA, TRAP staining, TRPV2 inhibitor Cell communication and signaling Medium 30326911
2023 Replication stress causes ssDNA/dsDNA to translocate to the cytoplasm, activating cGAS and producing cGAMP; cGAMP binding to STING causes its dissociation from TRPV2, derepressing TRPV2 and causing Ca2+ release from the ER, which activates CaMKK2/AMPK to protect replication forks from Exo1-mediated degradation. Genetic manipulation, biochemical co-immunoprecipitation (STING-TRPV2 interaction), Ca2+ measurements, epistasis analysis Molecular cell Medium 36696898
2022 TRPV2 in myeloid cells facilitates virus penetration by promoting cell membrane tension and mobility through the Ca2+-LRMDA axis; Ca2+-impermeable TRPV2-E572Q mutant fails to restore viral infection in TRPV2 KO cells; TRPV2 KO leads to downregulation of Lrmda and reduced membrane tension; LRMDA complementation restores membrane tension and viral penetration. TRPV2 conditional KO, reconstitution with TRPV2 or Ca2+-impermeable mutant, LRMDA knockdown/complementation, membrane tension and mobility assays Advanced science Medium 36261399
2018 Phagocytosis in primary human macrophages requires TRPV2-mediated Ca2+ influx; P. aeruginosa recruits TRPV2 to the cell surface; TRPV2 must be localized in lipid rafts to be functional for phagocytosis; CF macrophages display deficient TRPV2 function and impaired phagocytosis. Pharmacological inhibition of TRPV2, siRNA knockdown, phagocytosis assays, Ca2+ imaging, lipid raft fractionation Scientific reports Medium 29523858
2024 TRPV2 is highly expressed in B cells and required for B cell immunological synapse formation and activation; the pore and N-terminal domains are critical for cation permeation and mechanosensation; TRPV2 deficiency in B cells impairs antibody responses; TRPV2 activity promotes membrane potential depolarization and cytoskeleton remodeling during antigen stimulation. B cell-specific TRPV2 KO mice, immunological synapse imaging, antibody response assays, domain-specific mutagenesis The Journal of experimental medicine Medium 38353705
2019 TRPV2 silencing increases glioma (U87MG) cell proliferation, rescues cells from Fas-induced apoptosis, downregulates Fas and procaspase-8 expression, and upregulates Bcl-XL; these effects depend on ERK activation; ERK inhibition (PD98059) restores Akt/PKB activation, reduces Bcl-XL, promotes Fas expression, and increases apoptosis sensitivity in TRPV2-silenced cells. siRNA silencing, RT-Profiler PCR array, BrdU proliferation assay, flow cytometry apoptosis, ERK inhibitor PD98059 Carcinogenesis Medium 20093382
2023 TRPV2 localizes at the leading edge in dynamic nascent adhesions of invasive melanoma cells; TRPV2 activity regulates calcium-mediated activation of calpain and cleavage of talin, along with F-actin organization; TRPV2 silencing prevents aggressive migratory and invasive behavior; TRPV2 activity is sufficient to confer migratory and invasive potential. In vitro migration/invasion assays, in vivo mouse models, TRPV2 silencing, live-cell imaging of TRPV2 localization, calpain activity assays, talin cleavage Western blot, F-actin staining EMBO reports Medium 36744297
2019 TRPV2 stimulation in rheumatoid arthritis fibroblast-like synoviocytes reduces FLS adhesion, decreases integrin (αν, β1, β3) localization to plasma membrane, reduces activated RhoA and Rac1 levels, decreases cofilin activation, and inhibits invasion; RhoA activators overcome TRPV2-induced suppression. TRPV2 pharmacological stimulation, FLS adhesion and invasion assays, integrin surface localization, RhoA/Rac1 activity assays, cofilin western blotting International immunopharmacology Medium 30851707
2016 LL-37 activates TRPV2 and recruits it to pseudopodia via PI3K/AKT pathway activation, causing Ca2+ entry that cooperates with BKCa channel K+ efflux to drive cancer cell migration; LL-37 D-enantiomer has identical effects, suggesting membrane physical property modification rather than specific receptor binding is the mechanism. Ca2+ imaging, migration assays (wound healing), PI3K/AKT inhibition, D-enantiomer controls, confocal microscopy of TRPV2 localization Oncotarget Medium 26993604
2016 Heat sensitivity of TRPV2 exhibits strong use dependence: prior heat activation decreases activation temperature threshold, reduces slope sensitivity, and accelerates activation time courses. Prior heat sensitizes agonist responses, but agonist activation does not sensitize heat responses (non-reciprocal cross-use-dependence), indicating separate temperature sensing and agonist activation pathways. Electrophysiology (patch-clamp), quantitative thermal activation analysis Biophysical journal Medium 27074678
2019 TRPV2 channels mediate osmotic cell swelling-induced insulin secretion in mouse beta-cells; TRPV2 siRNA knockdown and tranilast reduce hypotonic stimulation-induced Ca2+ elevation and insulin secretion; glucose-stimulated insulin secretion is also reduced by TRPV2 knockdown. Ca2+ imaging, siRNA knockdown, tranilast pharmacology, insulin secretion ELISA from isolated islets American journal of physiology. Cell physiology Medium 30649920
2015 TRPV2 dominant-negative expressing skeletal muscle fibres show slower membrane depolarization, diminished Ca2+ response, smaller regulatory volume increase (RVI), and decreased SPAK phosphorylation in response to hyperosmotic shock, suggesting TRPV2 activation depolarizes T-tubules, triggering Ca2+ release from sarcoplasmic reticulum and activating SPAK/NKCC1 for RVI. TRPV2 dominant-negative overexpression in skeletal muscle fibres, Ca2+ imaging, membrane potential measurements, SPAK phosphorylation Western blot, BAPTA chelation The Journal of physiology Medium 26108786
2012 In the retinal pigment epithelium, TRPV2 mediates the sustained Ca2+ elevation phase of angiotensin II signaling; TRPV2 siRNA reduces the sustained phase of AngII-mediated Ca2+ transients by 53%; TRPV2 co-localizes with AT1R/Atrap complex; IGF-1 and CBD increase TRPV2 surface expression via PI3K. siRNA knockdown, Ca2+ imaging, SKF96365 pharmacology, immunostaining, co-localization analysis PloS one Medium 23185387
2015 In the retinal pigment epithelium, IGF-1 increases TRPV2 surface expression and channel activity via PI3K; CBD increases TRPV2 surface expression (more than IGF-1) and channel activity; PI3K inhibitor LY294002 abolishes both effects; heat further potentiates CBD- but not IGF-1-stimulated conductance. Whole-cell patch-clamp, confocal microscopy for surface TRPV2 quantification, PI3K inhibition, IGF-1 and CBD pharmacology in ARPE-19 cells Graefe's archive for clinical and experimental ophthalmology Medium 25616727
2003 VRL-1 (TRPV2) expressed in F-11 cells is N-glycosylated when overexpressed heterologously, similar to VR1; endogenous VRL-1 in F-11 cells shows mainly cytoplasmic localization by immunofluorescence, whereas overexpressed rat VRL-1 appears mainly at the plasma membrane. RT-PCR, deglycosylation assay (N-linked glycosylation), immunofluorescence localization European journal of biochemistry Low 14622291
2016 TRPV2 activation inhibits differentiation of brown adipocytes in a dose-dependent manner during early differentiation stages via a calcineurin pathway; mechanical force also inhibits differentiation through TRPV2; these effects are significantly reduced in TRPV2 KO cells and reversed by calcineurin inhibitors (cyclosporine A, FK506). TRPV2 KO mouse adipocytes, TRPV2 agonist/antagonist pharmacology, mechanical stimulation, calcineurin inhibitors, differentiation markers Pflugers Archiv Medium 27318696

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Cryo-electron microscopy structure of the TRPV2 ion channel. Nature structural & molecular biology 219 26779611
2001 Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2. Physiological genomics 181 11160995
2009 Lysophospholipids stimulate prostate cancer cell migration via TRPV2 channel activation. Biochimica et biophysica acta 161 19321128
2016 Structure of the full-length TRPV2 channel by cryo-EM. Nature communications 156 27021073
2013 What do we know about the transient receptor potential vanilloid 2 (TRPV2) ion channel? The FEBS journal 152 23615321
2011 Mast-cell degranulation induced by physical stimuli involves the activation of transient-receptor-potential channel TRPV2. Physiological research 149 21574765
2004 A TRPV2-PKA signaling module for transduction of physical stimuli in mast cells. The Journal of experimental medicine 128 15249591
2019 Molecular mechanism of TRPV2 channel modulation by cannabidiol. eLife 125 31566564
2007 Increased TRPA1, TRPM8, and TRPV2 expression in dorsal root ganglia by nerve injury. Biochemical and biophysical research communications 122 17517374
2008 Regulation of calcium-permeable TRPV2 channel by insulin in pancreatic beta-cells. Diabetes 115 18984736
2014 TRPV2 is critical for the maintenance of cardiac structure and function in mice. Nature communications 112 24874017
2010 TRPV2 channel negatively controls glioma cell proliferation and resistance to Fas-induced apoptosis in ERK-dependent manner. Carcinogenesis 93 20093382
2007 Transient receptor potential vanilloid type 2 (TRPV2) expression in normal urothelium and in urothelial carcinoma of human bladder: correlation with the pathologic stage. European urology 93 17977643
2010 Ca2+-dependent desensitization of TRPV2 channels is mediated by hydrolysis of phosphatidylinositol 4,5-bisphosphate. The Journal of neuroscience : the official journal of the Society for Neuroscience 92 20926660
2006 Expression of transient receptor potential vanilloid 1 (TRPV1) and 2 (TRPV2) in human peripheral blood. Molecular immunology 84 16777226
2005 Peripheral inflammation induces up-regulation of TRPV2 expression in rat DRG. Pain 80 16298071
2010 Involvement of TRPV2 activation in intestinal movement through nitric oxide production in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 78 21147993
2018 Conformational plasticity in the selectivity filter of the TRPV2 ion channel. Nature structural & molecular biology 77 29728656
2016 Lack of TRPV2 impairs thermogenesis in mouse brown adipose tissue. EMBO reports 76 26882545
2011 Differential TRPV1 and TRPV2 channel expression in dental pulp. Journal of dental research 74 21406609
2006 PI3-kinase promotes TRPV2 activity independently of channel translocation to the plasma membrane. Cell calcium 74 16533525
2019 Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2. Proceedings of the National Academy of Sciences of the United States of America 72 31719194
2013 Blockade of sarcolemmal TRPV2 accumulation inhibits progression of dilated cardiomyopathy. Cardiovascular research 72 23786999
2004 Immunoreactive TRPV-2 (VRL-1), a capsaicin receptor homolog, in the spinal cord of the rat. The Journal of comparative neurology 72 14961565
2020 TRPV2: A Cancer Biomarker and Potential Therapeutic Target. Disease markers 69 33376561
2016 Physiological significance of TRPV2 as a mechanosensor, thermosensor and lipid sensor. The journal of physiological sciences : JPS 68 26841959
2005 Heteromerization and colocalization of TrpV1 and TrpV2 in mammalian cell lines and rat dorsal root ganglia. Neuroreport 67 16237318
2018 Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts: alteration in macrophages from patients with cystic fibrosis. Scientific reports 66 29523858
2016 TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer. Oncotarget 66 30323891
2012 Expression and distribution of TRPV2 in rat brain. Experimental neurology 64 22750329
2019 Cannabidiol Increases Proliferation, Migration, Tubulogenesis, and Integrity of Human Brain Endothelial Cells through TRPV2 Activation. Molecular pharmaceutics 61 30721081
2007 2-Aminoethoxydiphenyl borate as a common activator of TRPV1, TRPV2, and TRPV3 channels. Handbook of experimental pharmacology 61 17217057
2001 Vanilloid receptor homologue, VRL1, is expressed by both A- and C-fiber sensory neurons. Neuroreport 61 11726776
2010 RANKL-induced TRPV2 expression regulates osteoclastogenesis via calcium oscillations. Cell calcium 59 20980052
2002 VRl- and VRL-l-like immunoreactivity in normal and injured trigeminal dental primary sensory neurons of the rat. Acta odontologica Scandinavica 59 12020118
2005 Formation of a physiological complex between TRPV2 and RGA protein promotes cell surface expression of TRPV2. Journal of cellular biochemistry 57 15547947
2015 Dystrophic cardiomyopathy: role of TRPV2 channels in stretch-induced cell damage. Cardiovascular research 56 25616416
2010 Insulin/phosphoinositide 3-kinase pathway accelerates the glucose-induced first-phase insulin secretion through TrpV2 recruitment in pancreatic β-cells. The Biochemical journal 56 20854263
2013 TRPV2 mediates adrenomedullin stimulation of prostate and urothelial cancer cell adhesion, migration and invasion. PloS one 55 23741410
2022 Structural insights into TRPV2 activation by small molecules. Nature communications 54 35484159
2014 TRPV2. Handbook of experimental pharmacology 51 24756709
2013 Astrocytes express functional TRPV2 ion channels. Biochemical and biophysical research communications 51 24161738
2018 Structures of TRPV2 in distinct conformations provide insight into role of the pore turret. Nature structural & molecular biology 50 30598551
2004 VR1-, VRL-1- and P2X3 receptor-immunoreactive innervation of the rat temporomandibular joint. Brain research 50 15081392
2016 Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2. Biophysical journal 49 27074678
2017 Esophageal cancer stem cells are suppressed by tranilast, a TRPV2 channel inhibitor. Journal of gastroenterology 48 28389731
2014 Loss of TRPV2 Homeostatic Control of Cell Proliferation Drives Tumor Progression. Cells 48 24709905
2007 Heat sensitization in skin and muscle nociceptors expressing distinct combinations of TRPV1 and TRPV2 protein. Journal of neurophysiology 48 17287441
2003 The co-expression of VR1 and VRL-1 in the rat vagal sensory ganglia. Brain research 48 12867271
2016 TRPV2 Channels Contribute to Stretch-Activated Cation Currents and Myogenic Constriction in Retinal Arterioles. Investigative ophthalmology & visual science 45 27784066
2023 Cytosolic DNA sensing by cGAS/STING promotes TRPV2-mediated Ca2+ release to protect stressed replication forks. Molecular cell 44 36696898
2022 Allosteric activation of the metabolic enzyme GPD1 inhibits bladder cancer growth via the lysoPC-PAFR-TRPV2 axis. Journal of hematology & oncology 44 35836291
2018 TRPV2-induced Ca2+-calcineurin-NFAT signaling regulates differentiation of osteoclast in multiple myeloma. Cell communication and signaling : CCS 44 30326911
2016 Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells. Oncotarget 44 26993604
2022 Cannabidiol Inhibits Tumorigenesis in Cisplatin-Resistant Non-Small Cell Lung Cancer via TRPV2. Cancers 43 35267489
2009 Ontogenetic expression of the vanilloid receptors TRPV1 and TRPV2 in the rat retina. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 43 19619635
2004 The co-expression of P2X3 receptor with VR1 and VRL-1 in the rat trigeminal ganglion. Brain research 43 14725976
2013 Targeting TRPV1 and TRPV2 for potential therapeutic interventions in cardiovascular disease. Translational research : the journal of laboratory and clinical medicine 42 23453732
2005 TRPV2, a capsaicin receptor homologue, is expressed predominantly in the neurotrophin-3-dependent subpopulation of primary sensory neurons. Neuroscience 42 15561438
2019 The expression and role of TRPV2 in esophageal squamous cell carcinoma. Scientific reports 39 31690728
2019 Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes. eLife 38 31090543
2016 Activation of TRPV2 negatively regulates the differentiation of mouse brown adipocytes. Pflugers Archiv : European journal of physiology 35 27318696
2022 Structural mechanisms of TRPV2 modulation by endogenous and exogenous ligands. Nature chemical biology 34 36163384
2010 Characterization of calmodulin binding domains in TRPV2 and TRPV5 C-tails. Amino acids 34 20686800
2012 Angiotensin-2-mediated Ca2+ signaling in the retinal pigment epithelium: role of angiotensin-receptor-associated-protein and TRPV2 channel. PloS one 33 23185387
2019 Mechanism for Regulation of Melanoma Cell Death via Activation of Thermo-TRPV4 and TRPV2. Journal of oncology 32 30881453
2004 Vanilloid receptor like 1 (VRL1) immunoreactivity in mammalian retina: colocalization with somatostatin and purinergic P2X1 receptors. The Journal of comparative neurology 31 15174083
2019 TRPV2 channels mediate insulin secretion induced by cell swelling in mouse pancreatic β-cells. American journal of physiology. Cell physiology 30 30649920
2015 Translocation of TRPV2 channel induced by focal administration of mechanical stress. Physiological reports 30 25677550
2013 The distribution of TRPV1 and TRPV2 in the rat pharynx. Cellular and molecular neurobiology 30 23584686
2003 Dual expression of mouse and rat VRL-1 in the dorsal root ganglion derived cell line F-11 and biochemical analysis of VRL-1 after heterologous expression. European journal of biochemistry 30 14622291
2021 TRPV2 Promotes Cell Migration and Invasion in Gastric Cancer via the Transforming Growth Factor-β Signaling Pathway. Annals of surgical oncology 28 34855064
2007 Distribution of TRPV1- and TRPV2-immunoreactive afferent nerve endings in rat trachea. Journal of anatomy 28 17979952
1995 Delineation of the virulence-related locus (vrl) of Dichelobacter nodosus. Microbiology (Reading, England) 28 7496519
2023 Cannabidiol sensitizes TRPV2 channels to activation by 2-APB. eLife 27 37199723
2022 The effects of cannabidiol via TRPV2 channel in chronic myeloid leukemia cells and its combination with imatinib. Cancer science 26 34971020
2021 Tranilast, a Transient Receptor Potential Vanilloid 2 Channel (TRPV2) Inhibitor Attenuates Amyloid β-Induced Cognitive Impairment: Possible Mechanisms. Neuromolecular medicine 26 34231190
2022 Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel. eLife 25 35686730
2022 The Transient Receptor Potential Vanilloid 2 (TRPV2) Channel Facilitates Virus Infection Through the Ca2+ -LRMDA Axis in Myeloid Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 25 36261399
2023 The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential. EMBO reports 24 36744297
2021 Tetrandrine Ameliorates Myocardial Ischemia Reperfusion Injury through miR-202-5p/TRPV2. BioMed research international 24 33763489
2020 Amelioration of diabetes-induced cognitive impairment by Transient Receptor Potential Vanilloid 2 (TRPV2) channel inhibitor: Behavioral and mechanistic study. Neurochemistry international 24 32652268
2019 TRPV2 suppresses Rac1 and RhoA activation and invasion in rheumatoid arthritis fibroblast-like synoviocytes. International immunopharmacology 24 30851707
2019 Blockade of TRPV2 is a Novel Therapy for Cardiomyopathy in Muscular Dystrophy. International journal of molecular sciences 24 31394715
2019 TRPV2 channel as a possible drug target for the treatment of heart failure. Laboratory investigation; a journal of technical methods and pathology 24 31857697
2017 Stretch-activated TRPV2 channels: Role in mediating cardiopathies. Progress in biophysics and molecular biology 24 28546113
2014 TRPV2 in the development of experimental colitis. Scandinavian journal of immunology 24 24965783
2019 Potential roles in cardiac physiology and pathology of the cation channel TRPV2 expressed in cardiac cells and cardiac macrophages: a mini-review. American journal of physiology. Heart and circulatory physiology 23 31809212
2023 Pharmacological inhibition of TRPV2 attenuates phagocytosis and lipopolysaccharide-induced migration of primary macrophages. British journal of pharmacology 22 37254803
2016 Polymorphisms of the TRPV2 and TRPV3 genes associated with fibromyalgia in a Korean population. Rheumatology (Oxford, England) 22 27079220
2022 Oxidative Stress-Induced TRPV2 Expression Increase Is Involved in Diabetic Cataracts and Apoptosis of Lens Epithelial Cells in a High-Glucose Environment. Cells 21 35406761
2024 Ion channel TRPV2 is critical in enhancing B cell activation and function. The Journal of experimental medicine 20 38353705
2019 The Transient Receptor Potential Vanilloid Type-2(TRPV2) Ion Channels in Neurogenesis andGliomagenesis: Cross-Talk between TranscriptionFactors and Signaling Molecules. Cancers 20 30845786
2019 Physiological and Pathological Role of TRPV1, TRPV2 and TRPV4 Channels in Heart. Current cardiology reviews 20 30848206
2016 Functional TRPV2 and TRPV4 channels in human cardiac c-kit(+) progenitor cells. Journal of cellular and molecular medicine 20 26865051
2015 Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres. The Journal of physiology 20 26108786
2009 TRPV2 expression in rat oral mucosa. Histochemistry and cell biology 20 19579031
2023 Tetrandrine downregulates TRPV2 expression to ameliorate myocardial ischemia/reperfusion injury in rats via regulation of cardiomyocyte apoptosis, calcium homeostasis and mitochondrial function. European journal of pharmacology 19 38061472
2015 Regulation of surface expression of TRPV2 channels in the retinal pigment epithelium. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 18 25616727
2005 Immunolocalization of VR1 and VRL1 in rat larynx. Autonomic neuroscience : basic & clinical 18 15620571

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