Affinage

TRPV3

Transient receptor potential cation channel subfamily V member 3 · UniProt Q8NET8

Length
790 aa
Mass
90.6 kDa
Annotated
2026-06-10
100 papers in source corpus 53 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRPV3 is a Ca2+-permeable, nonselective cation channel that functions as a polymodal sensor in skin keratinocytes and other epithelia, activated by warm temperatures (threshold ~33-39°C) and by chemical agonists including 2-APB, camphor, and a range of monoterpenes (PMID:12077604, PMID:12077606, PMID:15194687, PMID:15175387, PMID:15746429, PMID:17420775). The channel is steeply temperature-dependent and undergoes characteristic sensitization with repeated stimulation, a hysteresis intrinsic to channel gating that arises from relief of Ca2+/calmodulin-mediated inhibition acting at an N-terminal site (PMID:18178557, PMID:22006988). Distinct activation modalities are mechanistically separable and map to discrete structural determinants: pore-region S6 and adjacent residues control heat activation (PMID:19160498), cytoplasmic residues H426 and R696 control 2-APB sensitivity (PMID:19164517), pore cysteine C619 controls camphor sensitivity (PMID:23625413), and the intracellular TRP domain governs use-dependent temperature gating (PMID:28154143). Cryo-EM structures across closed, sensitized, open, and inactivated states establish that gating proceeds through α-to-π helical transitions in the pore-lining S6 helices and that agonists bind allosteric sites distal to the pore — including the vanilloid site and S1-S4/ARD-TMD linker sites — to converge on pore opening, with bound lipids stabilizing the closed selectivity filter (PMID:30127359, PMID:32572252, PMID:38691614); TRPV3 additionally adopts a pore-dilated pentameric assembly in dynamic equilibrium with the canonical tetramer (PMID:37648856). Channel activity is negatively regulated by intracellular protons sensed at H426 (PMID:22679014), by Mg2+ acting on both sides of the pore (PMID:22622423), by ATP competing with calmodulin at the N-terminal ankyrin repeat domain (PMID:19864432), by PI(4,5)P2 binding TRP-domain basic residues (PMID:21321070), by FIH-mediated asparaginyl hydroxylation at N242 as an oxygen-sensing input (PMID:25413349), and by the interacting protein TMEM79, which promotes its lysosomal degradation (PMID:37474531). In keratinocytes, TRPV3-mediated Ca2+ influx relays temperature information to sensory neurons via ATP release (PMID:19669158), drives proliferation through a Ca2+/CaMKII→TGFα/EGFR→PI3K→NF-κB cascade (PMID:32535744), regulates NOS-independent NO production and wound healing (PMID:21712817), and cooperates with PAR2 to convey itch (PMID:32004565). Beyond skin, TRPV3 mediates strontium-dependent oocyte egg activation (PMID:24316078) and contributes to cerebrovascular endothelial dilation (PMID:26453324). Gain-of-function missense mutations, most notably at Gly573, render the channel constitutively open and cause Olmsted syndrome, characterized by keratoderma, hair loss, and severe pruritus (PMID:22405088, PMID:36302896).

Mechanistic history

Synthesis pass · year-by-year structured walk · 33 steps
  1. 2002 High

    Establishing TRPV3 as a heat-activated Ca2+-permeable channel defined a new molecular thermosensor and raised the question of where it acts physiologically.

    Evidence Heterologous expression with calcium imaging and electrophysiology showing temperature-dependent cation conductance with hysteresis; co-expression modulation with TRPV1

    PMID:12077604 PMID:12077606

    Open questions at the time
    • Cellular site of action and in vivo role unresolved at this stage
    • Heteromerization with TRPV1 inferred from functional modulation, not structurally confirmed
  2. 2004 High

    Identifying 2-APB as the first chemical agonist gave a pharmacological handle to dissect activation independent of heat.

    Evidence Calcium imaging, electrophysiology, and inside-out single-channel recording in HEK293 and Xenopus oocytes showing increased open probability

    PMID:15175387 PMID:15194687

    Open questions at the time
    • Binding site for 2-APB not localized
    • Specificity over related TRPV channels limited
  3. 2005 High

    Localizing TRPV3 to keratinocytes and showing thermosensory deficits in null mice relocated the channel's primary role from sensory neurons to skin.

    Evidence Knockout mouse behavior, primary keratinocyte calcium imaging, camphor activation abolished in KO

    PMID:15746429

    Open questions at the time
    • Mechanism of keratinocyte-to-neuron signal transmission unknown
    • Molecular basis of camphor sensing not defined
  4. 2005 High

    Defining biphasic agonist currents and the role of pore residue D641 framed loss of divalent-cation inhibition as a key gating event.

    Evidence Whole-cell patch clamp, D641 mutagenesis, and ion substitution in HEK293 cells and keratinocytes

    PMID:15722340

    Open questions at the time
    • Physiological relevance of the I2 state unclear
    • Identity of the inhibitory divalent not fully resolved here
  5. 2006 High

    Recurrent Gly573 gain-of-function mutations causing hairless/dermatitis rodent phenotypes linked constitutive TRPV3 activity to skin and hair disease.

    Evidence Genetic mapping, sequencing, and heterologous electrophysiology in DS-Nh mice and WBN/Kob-Ht rats; transgenic and viability studies

    PMID:16858425 PMID:17706768

    Open questions at the time
    • Downstream cellular consequences of constitutive activity not yet mechanistically defined
    • Human disease relevance not yet established
  6. 2008 High

    Defining calmodulin/Ca2+ relief of inhibition explained the sensitization and hysteresis that distinguish TRPV3 gating.

    Evidence Whole-cell patch clamp, calmodulin-site and D641 mutagenesis, Ca2+ buffering and CaM inhibitors in HEK293

    PMID:18178557

    Open questions at the time
    • Whether sensitization is Ca2+-dependent or channel-intrinsic not yet resolved
  7. 2009 High

    Mutagenesis screens dissociated heat, 2-APB, and voltage activation into separable structural determinants, showing TRPV3 integrates multiple modalities through distinct sites.

    Evidence High-throughput random mutagenesis (~14,000 clones), site-directed mutagenesis and electrophysiology mapping S6/pore for heat and H426/R696 for 2-APB

    PMID:19160498 PMID:19164517

    Open questions at the time
    • How separate sites couple to a common gate not defined
    • Structural context absent
  8. 2009 High

    Showing heat-evoked ATP release from keratinocytes acting on DRG P2 receptors established the keratinocyte-to-neuron temperature relay.

    Evidence Keratinocyte-DRG and biosensor co-culture, ATP detection, P2 antagonists, TRPV3/TRPV1 KO mice

    PMID:19669158

    Open questions at the time
    • Mechanism of ATP release downstream of Ca2+ influx unknown
  9. 2009 Medium

    Mapping competing ATP and calmodulin binding to the ankyrin repeat domain identified the ARD as an integrating negative-regulatory hub.

    Evidence ARD-site mutagenesis with electrophysiology and calcium imaging in HEK293

    PMID:19864432

    Open questions at the time
    • Single-lab binding-site inference without direct structural confirmation
    • Stoichiometry of ATP/CaM competition not resolved
  10. 2011 High

    Excised-patch experiments established sensitization as intrinsic channel-gating hysteresis independent of extracellular Ca2+, refining the earlier CaM model.

    Evidence Inside-out and outside-out patch clamp with BAPTA/EGTA and non-buffering BAPTA-analog controls

    PMID:22006988

    Open questions at the time
    • Molecular conformational basis of hysteresis not yet structurally defined
  11. 2011 High

    Identifying PI(4,5)P2 as a direct inhibitor acting on TRP-domain basic residues placed TRPV3 under lipid and receptor-coupled control.

    Evidence Excised-patch electrophysiology, TRP-domain mutagenesis, PI4-kinase inhibition in keratinocytes and M1-receptor HEK293

    PMID:21321070

    Open questions at the time
    • Structural mode of PI(4,5)P2 binding not defined at this stage
  12. 2011 High

    Linking TRPV3 to NOS-independent NO production and migration connected the channel to keratinocyte wound healing.

    Evidence NO assays, in vitro migration, and TRPV3 KO wound healing and behavior

    PMID:21712817

    Open questions at the time
    • Biochemical route from Ca2+ influx to nitrite-dependent NO not fully resolved
  13. 2012 High

    Identifying human TRPV3 gain-of-function mutations as the cause of Olmsted syndrome established a direct Mendelian disease link via constitutive channel opening.

    Evidence Whole-exome sequencing of patient trios and electrophysiology of G573S/G573C/W692G mutants in HEK293

    PMID:22405088

    Open questions at the time
    • Cellular pathology connecting constitutive activity to keratoderma and hair loss not yet defined
  14. 2012 High

    Defining intracellular proton sensing at H426 and Mg2+ inhibition at pore residues extended the regulatory repertoire and tied channel activity to keratinocyte death.

    Evidence Patch clamp, single-channel recording, mutagenesis (H426, D641, E679, E682), and cell-death assays in HaCaT/CHO/keratinocytes

    PMID:22622423 PMID:22679014

    Open questions at the time
    • Physiological triggers of intracellular acidification and Mg2+ change in skin not defined
  15. 2013 High

    Demonstrating necessity and sufficiency of TRPV3 for strontium-dependent oocyte activation revealed a reproductive role distinct from skin sensing.

    Evidence Electrophysiology and calcium imaging in TrpV3 KO and WT oocytes with selective activation and Sr2+ assays; protein synthesis and actin-dependence studies

    PMID:24316078 PMID:26725171

    Open questions at the time
    • Mechanism coupling MII-stage trafficking and actin dependence to channel activity unresolved
  16. 2014 High

    Identifying FIH-mediated asparaginyl hydroxylation at N242 introduced oxygen sensing as a post-translational regulatory input to TRPV3.

    Evidence Mass spectrometry, N242 mutagenesis, FIH knockdown/inhibition, hypoxia, and electrophysiology

    PMID:25413349

    Open questions at the time
    • Physiological contexts where oxygen tension gates TRPV3 not established
  17. 2014 High

    Refined KO behavioral analyses constrained TRPV3's thermosensory role to innocuous warmth preference rather than acute heat nociception.

    Evidence TRPV3 and TRPV3/TRPV4 KO behavioral assays across backgrounds with pharmacological TRPV1 block

    PMID:21586160

    Open questions at the time
    • Compensation among thermoTRPs not fully excluded
    • Strain-dependence of phenotype unexplained
  18. 2017 High

    Chimeric analysis localizing use-dependence to a single TRP-domain residue implicated the TRP domain in temperature-gating behavior.

    Evidence Chimeras between use-dependent and use-independent homologs with single-residue mutagenesis and electrophysiology

    PMID:28154143

    Open questions at the time
    • How this residue couples to the temperature-sensing module mechanistically unresolved
  19. 2017 Medium

    Showing TRPV3 activation can suppress proliferation, induce death, and trigger NF-κB proinflammatory signaling in human keratinocytes highlighted context-dependent and inflammatory outputs.

    Evidence Calcium imaging, electrophysiology, cell death and NF-κB reporter assays in primary human keratinocytes

    PMID:28964718

    Open questions at the time
    • Single-lab study; reconciliation with proliferation-promoting roles not addressed
    • Stimulus intensity dependence of opposing outcomes unclear
  20. 2018 High

    Cryo-EM structures of closed and agonist-bound states defined the α-to-π S6 gating transition and distal allosteric agonist sites, providing the structural framework for activation.

    Evidence Cryo-EM of full-length mouse and human TRPV3 in apo, sensitized, and 2-APB/carvacrol-bound states

    PMID:30127359 PMID:30429472

    Open questions at the time
    • Lipid environment effects on conformations not yet incorporated
  21. 2018 High

    Defining the keratinocyte Ca2+/CaMKII→TGFα/EGFR→PI3K→NF-κB cascade gave the proliferative signaling pathway downstream of TRPV3.

    Evidence siRNA, KO mice, pathway inhibitors, TGFα ELISA, and phospho-protein Western blots in primary keratinocytes

    PMID:32535744

    Open questions at the time
    • How the same channel yields both proliferative and pro-death outcomes not reconciled
  22. 2018 Medium

    Linking TRPV3 to calcineurin/NFATc3 signaling implicated the channel in pathological cardiac hypertrophy.

    Evidence Western blot, Ca2+ measurement, NFATc3 translocation in neonatal rat cardiomyocytes and in vivo hypertrophy model

    PMID:30299584

    Open questions at the time
    • Single-lab finding; native cardiac expression and physiological activator not established
  23. 2019 High

    Engineering a vanilloid site into TRPV3 demonstrated conserved allosteric activation pathways across the TRPV family.

    Evidence Vanilloid-site mutagenesis, radioligand binding, and electrophysiology engineering RTx responsiveness

    PMID:30644819

    Open questions at the time
    • Endogenous role of the native vanilloid-site pocket in TRPV3 not defined
  24. 2020 High

    Lipid-nanodisc cryo-EM showed bound lipids stabilize the closed selectivity filter and revisited which S6 conformation marks closed versus activated states.

    Evidence Cryo-EM of human and mouse TRPV3 in lipid nanodiscs with electrophysiology

    PMID:32572252 PMID:32572254

    Open questions at the time
    • Identity of specific physiological lipids occupying these sites not resolved
  25. 2020 High

    Defining the TRPV3-PAR2 cooperation and TRPV3-dependent atopic dermatitis established the channel as an itch and inflammation effector in skin.

    Evidence TRPV3 KO scratching and neuronal activation assays, PAR2 pharmacology, human biopsy analysis, AD induction with osthole inhibition

    PMID:31308264 PMID:32004565

    Open questions at the time
    • Molecular nature of TRPV3-PAR2 functional coupling not defined
    • Whether interaction is direct or signaling-mediated unresolved
  26. 2020 Medium

    Correlating mutant biophysical severity with Olmsted syndrome phenotype connected gain-of-function magnitude to clinical outcome.

    Evidence Whole-cell patch clamp of multiple variants with homo- and heteromeric WT co-expression in HEK293

    PMID:32795529

    Open questions at the time
    • Single-lab genotype-phenotype correlation
    • In vivo validation of partial WT rescue not performed
  27. 2021 High

    Identifying pore-binding inhibitors (dyclonine) that rescue mutant-induced death advanced TRPV3 as a therapeutic target for pruritus and Olmsted syndrome.

    Evidence Single-channel electrophysiology, molecular simulation, mutagenesis, cell-death rescue, and in vivo itch model

    PMID:33876725

    Open questions at the time
    • Selectivity and in vivo efficacy in disease models not fully established
  28. 2021 High

    A G568V knock-in model linked gain-of-function TRPV3 to premature follicular keratinocyte differentiation and hair follicle stem cell loss, explaining Olmsted alopecia.

    Evidence Knock-in mouse histology, immunostaining, transcription factor analysis, and hair follicle stem cell assays

    PMID:33675791

    Open questions at the time
    • How constitutive Ca2+ entry drives the differentiation transcriptional program not detailed
  29. 2022 High

    Cryo-EM of the G573S mutant with the inhibitor Trpvicin revealed a dilated pore as the structural basis of gain-of-function and an inhibitor binding mode that remodels channel symmetry.

    Evidence Cryo-EM of WT and G573S TRPV3 with inhibitor plus in vivo itch and hair loss models

    PMID:36302896

    Open questions at the time
    • Generality of pore dilation across other Olmsted mutations not shown
  30. 2022 Medium

    Implicating proton-activated neuronal TRPV3 in ischemia/reperfusion neuronal death extended the channel's pathological roles to the CNS.

    Evidence siRNA, overexpression, electrophysiology of excitability/synaptic transmission, and MCA occlusion model with forsythoside B inhibition

    PMID:35646518

    Open questions at the time
    • Single-lab finding; native neuronal TRPV3 expression and synaptic localization not firmly established
  31. 2023 High

    Discovering a reversible pore-dilated pentameric assembly identified a non-canonical quaternary structure underlying TRPV3 pore dilation.

    Evidence High-speed AFM of membrane TRPV3 and cryo-EM of the pentamer with electrophysiology

    PMID:37648856

    Open questions at the time
    • Physiological prevalence and signaling consequences of the pentamer in native cells unknown
  32. 2023 High

    Identifying TMEM79 as a degradative negative regulator added a protein-level control point governing TRPV3 surface function and thermal preference.

    Evidence Heterologous co-expression, lysosomal trafficking assays, primary keratinocyte electrophysiology, and TMEM79 KO thermal preference behavior

    PMID:37474531

    Open questions at the time
    • Whether TMEM79 binds TRPV3 directly and the trafficking mechanism in full not defined
  33. 2024 High

    Structures with THCV and 2-APB defined two distinct agonist pockets (vanilloid site versus S1-S4/ARD-TMD linker) converging on common pore opening and revealed agonist-driven lipid displacement.

    Evidence Cryo-EM of human TRPV3 bound to THCV and 2-APB

    PMID:38691614

    Open questions at the time
    • How distinct binding events allosterically converge mechanistically not fully traced
    • Relevance of displaced apo-state lipid in vivo unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRPV3's many regulatory inputs (CaM, ATP, PI(4,5)P2, Mg2+, protons, O2/FIH, TMEM79, lipids) and its tetramer-pentamer equilibrium are integrated in native skin and other tissues to produce defined physiological outputs remains unresolved.
  • No unified model linking quaternary state to physiological signaling
  • Reconciliation of pro-proliferative versus pro-death keratinocyte outcomes not achieved
  • Endogenous activating ligands and their tissue contexts incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0140299 molecular sensor activity 4 GO:0005215 transporter activity 3
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-9709957 Sensory Perception 3 R-HSA-1266738 Developmental Biology 2
Partners
FIHPAR2TMEM79TRPV1

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 TRPV3 (VRL3) is a heat-activated, calcium-permeable nonselective cation channel with a temperature threshold of ~39°C. Increasing temperature from 22°C to 40°C in cells transfected with hTRPV3 elevated intracellular calcium by activating a cationic conductance. Current was steeply temperature-dependent, sensitized with repeated heating, and displayed hysteresis on heating and cooling. Heterologous expression in mammalian cells, calcium imaging, electrophysiology Nature High 12077604 12077606
2002 TRPV3 (VRL3) can associate with TRPV1 to form heteromeric vanilloid receptor channels, potentially modulating TRPV1 responses. TRPV3 is heat-sensitive but capsaicin-insensitive, and the gene is adjacent to VR1 on the chromosome. Heterologous co-expression, functional assays showing modulation of TRPV1 responses Nature Medium 12077606
2004 2-aminoethoxydiphenyl borate (2-APB) directly activates TRPV3 (as well as TRPV1 and TRPV2) expressed in HEK293 cells, and potentiates heat activation of TRPV3 in Xenopus oocytes. 2-APB is the first identified chemical activator of TRPV3. Calcium imaging and electrophysiology in HEK293 cells and Xenopus oocytes; inside-out patch recording showing increased TRPV3 open probability The Journal of biological chemistry / The Journal of neuroscience High 15175387 15194687
2005 TRPV3 is expressed in mouse keratinocytes (not primarily sensory neurons) and is required for normal thermosensory responses. TRPV3 null mice have strong deficits in responses to innocuous and noxious heat. Camphor specifically activates TRPV3 in keratinocytes; this activation was abolished in TRPV3-null mice, identifying TRPV3 as the camphor receptor in skin. Knockout mouse behavioral studies, primary keratinocyte calcium imaging, genetic ablation Science High 15746429
2005 Strong TRPV3 activation by agonists leads to biphasic currents (I1 and I2 phases). The I1-to-I2 transition involves larger current amplitude, loss of outward rectification, altered cation permeability, and changed sensitivity to blockers. Mutation of pore-loop residue Asp641 facilitated this transition; removal of extracellular divalent cations mimicked I2, suggesting the transition results from agonist/time-dependent loss of divalent cation inhibition. Whole-cell patch clamp, site-directed mutagenesis (D641 in pore loop), ion substitution experiments in HEK293 cells and primary keratinocytes The Journal of biological chemistry High 15722340
2006 Gain-of-function mutations at Gly573 (G573S and G573C) in TRPV3 cause constitutive channel activity, reduced temperature threshold, and hair loss/dermatitis in DS-Nh mice and WBN/Kob-Ht rats. The spontaneous mutations were identified as the cause of the hairless phenotype in these rodent strains. Genetic mapping, amino acid sequencing, heterologous expression in HEK293 and Xenopus oocytes with electrophysiology The Journal of investigative dermatology High 16858425
2006 Arachidonic acid and other unsaturated fatty acids directly potentiate 2APB-induced TRPV3 responses. This potentiation does not require AA metabolism (non-metabolizable AA analogs are equally effective) and is not blocked by PKC inhibitors, suggesting direct fatty acid action on the channel rather than through a kinase pathway. Calcium imaging, whole-cell and two-electrode voltage clamp, single-channel recording in excised patches (inside-out and outside-out) in HEK293 cells, Xenopus oocytes, and mouse keratinocytes Journal of cellular physiology High 16557504
2007 The G573S and G573C TRPV3 mutations render the channel constitutively active in heterologous systems and cause cell death in HEK293 cells. Co-expression of mutant with wild-type TRPV3 in Xenopus oocytes reduces temperature threshold and enhances wild-type responses, but the mutant itself is irresponsive to additional thermal/chemical stimuli. Electrophysiology in HEK293 cells and Xenopus oocytes, cell viability assays Cell calcium High 17706768
2007 Six monoterpenes (6-tert-butyl-m-cresol, carvacrol, dihydrocarveol, thymol, carveol, (+)-borneol) activate TRPV3 with EC50 values up to 16-fold lower than camphor. A ring-located hydroxyl group is a structural requirement for TRPV3 activation; none of these compounds activates TRPM8 to a major extent. Whole-cell patch clamp in HEK293 cells, dose-response curves in Xenopus oocytes British journal of pharmacology Medium 17420775
2008 TRPV3 sensitization to repetitive stimulation is mediated by calcium-dependent relief of channel inhibition. Calmodulin acts at an N-terminal site (residues 108-130) to inhibit TRPV3, and extracellular Ca2+ inhibition involves pore-loop residue Asp641. During sensitization, voltage dependence shifts to more negative potentials and the channel uncouples from voltage sensing. Increasing intracellular Ca2+ buffering strength or inhibiting calmodulin decreases sensitization. Whole-cell patch clamp, site-directed mutagenesis (D641N, calmodulin-binding site mutants), BAPTA/EGTA buffering, calmodulin inhibitors in HEK293 cells The Journal of biological chemistry High 18178557
2008 TRPV3 gain-of-function mutation G573S causes increased nerve growth factor responses to heat in keratinocytes. Transgenic mice expressing TRPV3(G573S) spontaneously develop allergic and pruritic dermatitis, demonstrating that TRPV3 activation in keratinocytes drives pruritus and dermatitis. Transgenic mouse model, histological/serological analysis, physiological measurement of NGF response to heat The Journal of investigative dermatology High 18754035
2008 The sixth transmembrane helix (S6) and adjacent extracellular pore loop of TRPV3 are specifically required for heat activation. A random mutagenesis screen of ~14,000 clones identified five single-point mutations in this pore region that abolish heat activation but do not perturb chemical activation or voltage modulation, demonstrating that temperature sensitivity is separable from other activation mechanisms. High-throughput random mutagenesis screen (~14,000 mutant clones), calcium imaging, electrophysiology Nature neuroscience High 19160498
2009 Two specific cytoplasmic residues, H426 (N-terminal) and R696 (TRP box), are required for TRPV3 sensitivity to 2-APB but not to camphor or voltage. Mutating these two residues in the 2-APB-insensitive TRPV4 to TRPV3 sequences was sufficient to induce TRPV3-like 2-APB sensitivity, demonstrating that 2-APB activation is separable from other activation mechanisms and depends on these two cytoplasmic residues. High-throughput mutagenesis (~14,000 clones), site-directed mutagenesis, calcium imaging, electrophysiology in HEK293 cells and Xenopus oocytes PNAS High 19164517
2009 TRPV3 in keratinocytes mediates temperature information to sensory neurons via ATP release. Heat-activated keratinocytes release ATP; ATP release is compromised in keratinocytes from TRPV3-deficient mice. ATP acts on P2 purinoreceptors on DRG neurons to convey temperature signals. Co-culture of keratinocytes with DRG neurons and P2X2-transfected HEK293 biosensor cells; ATP measurement; P2 receptor antagonist pharmacology; TRPV3 and TRPV1 knockout mice Pflugers Archiv High 19669158
2009 ATP and calmodulin share a conserved binding site on the TRPV3 N-terminal ankyrin repeat domain (ARD). ATP reduces TRPV3 sensitivity (in contrast to TRPV1 and TRPV4 where ATP sensitizes), and this effect requires an intact ARD binding site. Competing interactions of ATP and calmodulin at the ARD thus regulate TRPV3 sensitivity. Mutagenesis of ARD binding site, electrophysiology, calcium imaging in HEK293 cells The Journal of biological chemistry Medium 19864432
2009 TRPV3 is functionally expressed in corneal epithelial cells. Carvacrol activated primary mouse corneal epithelial cells and HCE-T cells via TRPV3; this was blocked by ruthenium red. Appropriate calcium influx via activated TRPV3 in corneal epithelial cells accelerated cell proliferation (wound healing assay). Calcium imaging, wound healing assay, ruthenium red pharmacology in primary corneal epithelial cells and HCE-T cells Experimental eye research Medium 19793539
2010 Farnesyl pyrophosphate (FPP), an endogenous intermediate of the mevalonate pathway, specifically activates TRPV3 among six thermoTRPs. FPP shifts voltage-dependence of TRPV3 as the activation mechanism. Intraplantar FPP injection elicits nociceptive behaviors in inflamed animals, and FPP-evoked keratinocyte signals are transmitted to sensory neurons in co-culture. Calcium imaging, voltage-clamp electrophysiology in HEK293 cells, cultured keratinocytes and sensory neurons; co-culture signaling assay; in vivo nociceptive behavior The Journal of biological chemistry High 20395302
2011 TRPV3 sensitization to repeated stimulation is intrinsic to the channel itself, arising from hysteresis of channel gating, independent of extracellular Ca2+. This was demonstrated in inside-out and outside-out excised membrane patches. BAPTA (but not EGTA) accelerates sensitization by directly potentiating channel gating, and BAPTA analogues lacking Ca2+-buffering capability also potentiate, indicating direct channel interaction. Excised inside-out and outside-out patch-clamp electrophysiology, BAPTA/EGTA/BAPTA-analog pharmacology The Journal of general physiology High 22006988
2011 Receptor-mediated hydrolysis of PI(4,5)P2 potentiates TRPV3 channel activity by causing a negative shift in voltage dependence, increasing voltage-independent current, and lowering thermal activation threshold. PI(4,5)P2 directly inhibits TRPV3 through interaction with basic residues in the TRP domain; neutralizing mutations in these residues abrogate the PI(4,5)P2 effect. Electrophysiology of native TRPV3 in primary human keratinocytes and expressed TRPV3 in M1-receptor-expressing HEK293 cells; excised patch recordings; mutagenesis of TRP domain basic residues; PI 4-kinase inhibition The Journal of general physiology High 21321070
2011 TRPV3 activation in keratinocytes induces nitric oxide (NO) production via a nitrite-dependent, NOS-independent pathway. TRPV3 and nitrite are involved in keratinocyte migration in vitro and in wound healing and thermosensory behaviors in vivo, as shown with TRPV3 knockout mice. NO detection assays in keratinocytes, TRPV3 knockout mouse wound healing and behavioral assays, in vitro keratinocyte migration Nature communications High 21712817
2011 Isopentenyl pyrophosphate (IPP), an upstream mevalonate-pathway metabolite, acts as a dual inhibitor of TRPV3 and TRPA1. IPP suppressed responses to specific agonists of TRPA1 and TRPV3 in HEK293 cells, sensory neurons, and keratinocytes; peripheral IPP attenuated TRPV3/TRPA1 agonist-specific acute pain behaviors in vivo. Calcium imaging, voltage-clamp electrophysiology, in vivo pain behavior, peripheral injection Pain Medium 21353389
2012 Gain-of-function missense mutations in TRPV3 (p.Gly573Ser, p.Gly573Cys, p.Trp692Gly) cause Olmsted syndrome. HEK293 cells expressing these mutants show much larger inward currents due to constitutive channel opening. Whole-exome sequencing of patient-parent trios, Sanger sequencing; electrophysiology in HEK293 cells expressing TRPV3 mutants American journal of human genetics High 22405088
2012 Intracellular acidification (induced by glycolic acid/alpha-hydroxy acids) directly activates TRPV3 via intracellular proton sensing. Histidine residue H426 in the N-terminal region is critical for sensing intracellular protons; H426 mutation abolished proton-mediated TRPV3 activation. TRPV3 activation by protons promotes keratinocyte death. Patch-clamp electrophysiology, cell death assay in HaCaT keratinocytes and HEK293 cells; site-directed mutagenesis of H426 The Journal of biological chemistry High 22679014
2012 Extracellular and intracellular Mg2+ tonically inhibit TRPV3 by acting on both sides of the pore loop. Extracellular Mg2+ inhibition involves pore-loop residue D641; intracellular Mg2+ inhibition involves E679 and E682 in the inner pore region. Mg2+ inhibits single-channel conductance but not open probability in TRPV3-expressing CHO cells. Single-channel recording in CHO cells, site-directed mutagenesis (D641, E679, E682), intracellular calcium assays in primary keratinocytes The Journal of investigative dermatology High 22622423
2013 TRPV3 is required for LTD at excitatory synapses on hippocampal s. radiatum interneurons and for LTP in CA1. Loss of interneuron LTD in TRPV3 KO mice disinhibits the circuit, resulting in attenuated pyramidal cell LTP; blocking GABA inhibition rescues LTP in TRPV3 KO slices. Hippocampal slice electrophysiology with TRPV3 KO mice; GABA blockade rescue experiment Hippocampus Medium 23536486
2013 TRPV3 in mouse oocytes mediates strontium influx required for egg activation. TRPV3 current is highest at metaphase II (MII, the stage of fertilization). TrpV3-knockout eggs fail to conduct Sr2+ and do not undergo strontium-induced activation. Selective TRPV3 activation provokes egg activation via massive Ca2+ entry. Electrophysiology and calcium imaging in TrpV3 KO and WT oocytes; TRP channel agonist stimulation; strontium activation assay Cell reports High 24316078
2013 Cholesterol sensitizes TRPV3 to lower temperatures and lower concentrations of chemical activators. Cholesterol supplementation robustly potentiated TRPV3 channel activity; this was reproduced in HaCaT keratinocytes natively expressing TRPV3. The effect was not due to increased plasma membrane targeting. Electrophysiology, calcium imaging in HEK293 cells and HaCaT keratinocytes; cholesterol manipulation; TIRF/cell surface expression controls Cell calcium Medium 24406294
2013 Camphor activates TRPV3 by interacting with pore-region cysteine residues. Mutation C619S abolished camphor sensitivity of TRPV3 while retaining responses to 2-APB and dihydrocarveol; C612S showed only minor reduction. Thus C619 is specifically required for camphor sensitivity. Site-directed mutagenesis of pore-region cysteines (C612S, C619S), two-electrode voltage clamp in Xenopus oocytes Pakistan journal of pharmaceutical sciences Medium 23625413
2014 TRPV3 null mice on the 129S6 background show impaired innocuous warm temperature preference (more restrictive range centered around cooler temperatures) but no deficits in acute heat nociception. TRPV3 and TRPV4 double KO mice on C57BL6 showed little change in heat nociception or inflammatory heat hyperalgesia, even when TRPV1 was also blocked. KO mouse behavioral studies (thermal gradient, hot plate, tail flick); pharmacological TRPV1 block; two background strains Molecular pain High 21586160
2014 Oxygen-dependent asparaginyl hydroxylation of TRPV3 at Asparagine 242 (within the ankyrin repeat domain) by the enzyme FIH (Factor Inhibiting HIF) inhibits TRPV3 activity. Hypoxia, FIH inhibitors, and N242 mutation all potentiate TRPV3-mediated current without altering TRPV3 protein levels, establishing a novel oxygen-sensing mechanism for channel regulation. Electrophysiology in TRPV3-expressing cells; FIH knockdown/inhibition; site-directed mutagenesis of N242; hypoxia experiments; mass spectrometry confirming hydroxylation Journal of cell science High 25413349
2014 TRPV3 promotes oral epithelial cell proliferation and wound healing in a temperature-dependent manner. Temperatures above 33°C activated TRPV3 and promoted oral epithelial cell proliferation; wound closure was delayed in TRPV3 KO mice. TRPV3 mRNA was upregulated in wounded tissues. TRPV3 KO mice tooth extraction model, proliferation assays, qRT-PCR, temperature stimulation of oral epithelial cells FASEB journal High 25351988
2015 TRPV3 channels in cerebrovascular endothelial cells mediate unitary Ca2+ influx events (TRPV3 sparklets) that cause dilation of cerebral parenchymal arterioles via activation of IK and SK Ca2+-activated K+ channels. Carvacrol-induced dilation was blocked by the selective TRPV3 blocker IPP and was nearly abolished by endothelium removal or IK/SK channel block. Total internal reflection fluorescence (TIRF) microscopy for sparklet imaging; pressure myography; IPP pharmacology; endothelium removal; IK/SK channel blockers American journal of physiology. Heart and circulatory physiology High 26453324
2015 TRPV3 protein is synthesized and translocated to the plasma membrane during oocyte maturation, reaching peak expression/activity at MII. TRPV3 channel activity in oocytes depends on an intact actin cytoskeleton. 2-APB at concentrations that promote Ca2+ influx in eggs specifically targets TRPV3 without blocking IP3R1. dsRNA knockdown, TRPV3 overexpression, protein synthesis inhibitors; calcium imaging; actin cytoskeleton disruption in mouse oocytes Cell calcium Medium 26725171
2017 A single residue difference between use-dependent and use-independent TRPV3 homologs determines the high initial temperature threshold and use-dependence of heat sensitivity. Restoring this single residue in the intracellular TRP domain region largely eliminates use-dependence, implicating the TRP domain in temperature-dependent gating. Chimeric channel construction between use-dependent and use-independent TRPV3 homologs; single-residue mutagenesis; electrophysiology PNAS High 28154143
2017 TRPV3 stimulation in human epidermal keratinocytes activates a Ca2+-permeable ion channel, suppresses keratinocyte proliferation, induces cell death, and triggers a proinflammatory response via the NF-κB pathway. Calcium imaging, electrophysiology, cell death assays, NF-κB reporter assays in primary human keratinocytes The Journal of investigative dermatology Medium 28964718
2018 Cryo-EM structures of full-length mouse TRPV3 in closed apo and agonist-bound open states reveal the gating mechanism. The agonist (2-APB/carvacrol) binds three allosteric sites distal to the pore. Channel opening involves α-to-π helical transitions in pore-lining S6 helices, elongation, rotation, and splaying of S6 in the open state. In the closed state, S6 is entirely α-helical and hydrophobically seals the pore. Cryo-electron microscopy of full-length mouse TRPV3 in apo and agonist-bound states Nature structural & molecular biology High 30127359
2018 Cryo-EM structures of apo and sensitized human TRPV3 and multiple 2-APB-bound conformations reveal α-to-π helix transitions in S6 during sensitization and a critical role for the S4-S5 linker π-helix during ligand-dependent gating. Cryo-electron microscopy of human TRPV3 in apo, sensitized, and 2-APB-bound states Nature communications High 30429472
2018 TRPV3 activation promotes keratinocyte proliferation through a Ca2+/CaMKII→TGFα/EGFR→PI3K→NF-κB signaling cascade. Carvacrol-stimulated Ca2+ influx via TRPV3 stimulates TGFα release and EGFR/PI3K/NF-κB phosphorylation; these effects are abolished by TRPV3 silencing and CaMKII inhibition. siRNA knockdown, TRPV3 KO mice, pharmacological inhibitors (CaMKII, EGFR, PI3K, NF-κB), TGFα ELISA, Western blot for phosphoproteins, primary keratinocytes Cell biology and toxicology High 32535744
2018 Activation of TRPV3 in cardiomyocytes aggravates pathological cardiac hypertrophy via a calcineurin/NFATc3 signaling pathway. TRPV3 activation increased intracellular Ca2+, promoted calcineurin and phospho-CaMKII expression, and enhanced NFATc3 nuclear translocation; blocking/knockdown of TRPV3 inhibited these responses. Western blot, intracellular Ca2+ measurement, NFATc3 nuclear translocation assay in neonatal rat cardiomyocytes; in vivo rat cardiac hypertrophy model Journal of cellular and molecular medicine Medium 30299584
2019 Six residues corresponding to the vanilloid-binding site in TRPV1 can be mutated in TRPV3 to engineer resiniferatoxin (RTx) binding. However, robust RTx-induced activation of TRPV3 additionally requires facilitation of channel opening by pore mutations, temperatures >30°C, or agonist sensitization, demonstrating conserved allosteric pathways for activation across the TRPV family. Site-directed mutagenesis of vanilloid site residues in TRPV3; radioligand binding; electrophysiology eLife High 30644819
2020 Cryo-EM structures of human TRPV3 in lipid nanodiscs reveal that lipids bound to the pore domain stabilize the selectivity filter in a narrow state and that both the selectivity filter and helix bundle crossing are constrictions in the closed state. Upon activation, both expand. In the inactivated state, the pore-lining helix becomes entirely α-helical (vs. π-helical in closed and open states). Cryo-electron microscopy of human TRPV3 in lipid nanodiscs; electrophysiological characterization Nature structural & molecular biology High 32572252
2020 Lipid nanodisc-reconstituted mouse TRPV3 cryo-EM structure shows that in the closed state, the S6 helix adopts a π-helical conformation (without agonist/sensitization), stabilized by intramolecular hydrogen bonds and lipid binding. Lipids at the pore domain stabilize the selectivity filter in a narrow state. This contrasts with prior detergent-based structures where π-helix was proposed as an activated feature. Cryo-electron microscopy of mouse TRPV3 reconstituted in lipid nanodiscs at 3.3 Å resolution Nature structural & molecular biology High 32572254
2020 TRPV3 and PAR2 in keratinocytes act together to convey itch information. Keratinocytes lacking TRPV3 impair PAR2 function, reducing neuronal activation and scratching behavior in response to PAR2 agonists. TRPV3 and PAR2 are both upregulated in atopic dermatitis skin from patients and mice. TRPV3 KO mouse scratching assays; neuronal activation assays; PAR2 agonist pharmacology; human skin biopsy analysis The Journal of investigative dermatology High 32004565
2020 TRPV3 inhibition attenuates atopic dermatitis. Pharmacological activation of TRPV3 with carvacrol caused AD development in wild-type mice but not TRPV3 KO mice. TRPV3 protein and inflammatory factors TNF-α/IL-6 were upregulated in the AD model. Inhibition with osthole reversed severity and reduced inflammatory factor expression. TRPV3 KO mice, chemical induction of AD model, Western blot, immunostaining, pharmacological inhibition with osthole Molecular pharmacology High 31308264
2020 TRPV3 gain-of-function mutations cause constitutively elevated basal open probability and increased voltage sensitivity that correlates with clinical severity of Olmsted syndrome. Functional changes are particularly pronounced in variants associated with severe OS (e.g., L673F, W692S) and milder in variants associated with mild OS (e.g., R416Q). Wild-type TRPV3 can partially rescue mutant channel function in vitro in proportion to clinical severity. Electrophysiology (whole-cell patch clamp) of TRPV3 variants expressed in HEK293 cells; homomeric and heteromeric co-expression with WT The Journal of investigative dermatology Medium 32795529
2021 Dyclonine (a clinical local anesthetic) inhibits TRPV3 by reducing open probability without affecting unitary conductance. Key residues in the TRPV3 pore region toggle inhibitory efficiency of dyclonine (identified by molecular simulations and mutagenesis). Dyclonine rescues cell death caused by gain-of-function TRPV3 mutations and suppresses pruritus in vivo. Single-channel electrophysiology, molecular docking/simulation, site-directed mutagenesis, gain-of-function TRPV3 cell death rescue assay, in vivo mouse itch model eLife High 33876725
2021 TRPV3 gain-of-function mutation G568V causes premature differentiation of follicular keratinocytes (precocious degeneration of trichohyalin/keratins, elevated apoptosis, attenuated Foxn1/Msx2/Dlx3/Gata3 transcription regulators), accelerated hair cycle, reduction of hair follicle stem cells, and miniaturized regenerated follicles, mechanistically explaining hair loss in Olmsted syndrome. Knock-in G568V mouse model, histology, immunostaining, transcription factor analysis, hair follicle stem cell assays The Journal of investigative dermatology High 33675791
2022 Cryo-EM structures of TRPV3 and the pathogenic G573S mutant complexed with inhibitor Trpvicin reveal that Trpvicin stabilizes TRPV3 in a closed state by binding to a specific site. The G573S mutant structure demonstrates that this mutation causes a dilated pore constituting the structural basis of gain-of-function activity. Trpvicin accesses additional binding sites inside the G573S central cavity to remodel channel symmetry and block the channel. Cryo-electron microscopy of WT and G573S mutant TRPV3 complexed with inhibitor; in vivo mouse itch and hair loss models Nature chemical biology High 36302896
2022 Neuronal TRPV3 channels activated by intracellular protons play a causative role in progressive neuronal cell death after cerebral ischemia/reperfusion injury. TRPV3 silencing reduces intrinsic neuronal excitability and excitatory synaptic transmissions; TRPV3 overexpression increases these and aggravates injury. Inhibition by forsythoside B decreases neural excitability and attenuates ischemic injury. siRNA knockdown and TRPV3 overexpression in mouse neurons; electrophysiology (excitability, synaptic transmission); transient MCA occlusion in vivo model Acta pharmaceutica Sinica. B Medium 35646518
2023 TRPV3 can form a pentameric assembly (in addition to the canonical tetramer) in the membrane. The pentameric state is in dynamic equilibrium with the tetramer via membrane diffusive protomer exchange, is reversible, and its population increases upon addition of the TRPV3 pore-dilation agonist DPBA. The cryo-EM structure of the TRPV3 pentamer shows an enlarged pore compared to the tetramer, identifying the pentamer as the structural correlate of pore dilation. High-speed atomic force microscopy (HS-AFM) of membrane-embedded TRPV3; cryo-EM structure of pentamer; electrophysiology Nature High 37648856
2023 TMEM79 acts as a negative regulator of TRPV3. Heterologous TMEM79 expression suppresses TRPV3-mediated currents in HEK293T cells. TMEM79 modulates TRPV3 translocalization and promotes its degradation in lysosomes. TRPV3-mediated currents and Ca2+ influx are potentiated in primary keratinocytes lacking TMEM79. TMEM79-deficient male mice prefer higher temperatures due to elevated TRPV3 function. Heterologous co-expression in HEK293T cells; TMEM79 KO mouse thermal preference assay; primary keratinocyte electrophysiology and calcium imaging; lysosomal trafficking assay Nature communications High 37474531
2024 Cryo-EM structures of wild-type human TRPV3 bound to THCV (cannabinoid) and 2-APB reveal two distinct agonist binding sites: THCV binds the vanilloid site, while 2-APB binds to the S1-S4 base and ARD-TMD linker sites. Despite binding distally located sites, both agonists induce similar pore opening and cause dissociation of a lipid occupying the vanilloid site in the apo state, revealing different but converging allosteric pathways. Cryo-electron microscopy of human TRPV3 bound to THCV and 2-APB Science advances High 38691614

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 701 12077604
2002 TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 642 12077606
2005 Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science (New York, N.Y.) 552 15746429
2004 2-aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2, and TRPV3. The Journal of biological chemistry 422 15194687
2012 Exome sequencing reveals mutations in TRPV3 as a cause of Olmsted syndrome. American journal of human genetics 270 22405088
2004 2-aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3. The Journal of neuroscience : the official journal of the Society for Neuroscience 242 15175387
2011 Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta physiologica (Oxford, England) 236 21726418
2007 Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy. BMC neurology 222 17521436
2009 TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP. Pflugers Archiv : European journal of physiology 204 19669158
2007 Monoterpenoid agonists of TRPV3. British journal of pharmacology 197 17420775
2018 Structure and gating mechanism of the transient receptor potential channel TRPV3. Nature structural & molecular biology 158 30127359
2006 Association of a mutation in TRPV3 with defective hair growth in rodents. The Journal of investigative dermatology 157 16858425
2009 Differential regulation of TRPV1, TRPV3, and TRPV4 sensitivity through a conserved binding site on the ankyrin repeat domain. The Journal of biological chemistry 149 19864432
2011 TRPV3 and TRPV4 ion channels are not major contributors to mouse heat sensation. Molecular pain 146 21586160
2008 Impact of the Gly573Ser substitution in TRPV3 on the development of allergic and pruritic dermatitis in mice. The Journal of investigative dermatology 144 18754035
2008 Pore region of TRPV3 ion channel is specifically required for heat activation. Nature neuroscience 143 19160498
2005 Biphasic currents evoked by chemical or thermal activation of the heat-gated ion channel, TRPV3. The Journal of biological chemistry 130 15722340
2006 Potentiation of TRPV3 channel function by unsaturated fatty acids. Journal of cellular physiology 118 16557504
2005 Increased capsaicin receptor TRPV1 in skin nerve fibres and related vanilloid receptors TRPV3 and TRPV4 in keratinocytes in human breast pain. BMC women's health 115 15755319
2010 Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3. The Journal of biological chemistry 111 20395302
2011 TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin. Nature communications 109 21712817
2018 Conformational ensemble of the human TRPV3 ion channel. Nature communications 102 30429472
2008 Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 99 18492727
2013 TRPV3: time to decipher a poorly understood family member! The Journal of physiology 97 23836684
2020 PAR2 Mediates Itch via TRPV3 Signaling in Keratinocytes. The Journal of investigative dermatology 94 32004565
2009 Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4. Proceedings of the National Academy of Sciences of the United States of America 93 19164517
2008 Calcium plays a central role in the sensitization of TRPV3 channel to repetitive stimulations. The Journal of biological chemistry 93 18178557
2017 Activation of TRPV3 Regulates Inflammatory Actions of Human Epidermal Keratinocytes. The Journal of investigative dermatology 91 28964718
2009 Intragastric administration of TRPV1, TRPV3, TRPM8, and TRPA1 agonists modulates autonomic thermoregulation in different manners in mice. Bioscience, biotechnology, and biochemistry 91 19420725
2011 Voltage- and temperature-dependent activation of TRPV3 channels is potentiated by receptor-mediated PI(4,5)P2 hydrolysis. The Journal of general physiology 83 21321070
2014 The thermosensitive TRPV3 channel contributes to rapid wound healing in oral epithelia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 82 25351988
2011 Hysteresis of gating underlines sensitization of TRPV3 channels. The Journal of general physiology 79 22006988
2007 The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active. Cell calcium 74 17706768
2011 Isopentenyl pyrophosphate is a novel antinociceptive substance that inhibits TRPV3 and TRPA1 ion channels. Pain 72 21353389
2015 Unitary TRPV3 channel Ca2+ influx events elicit endothelium-dependent dilation of cerebral parenchymal arterioles. American journal of physiology. Heart and circulatory physiology 70 26453324
2009 Functional expression of transient receptor potential vanilloid 3 (TRPV3) in corneal epithelial cells: involvement in thermosensation and wound healing. Experimental eye research 69 19793539
2016 Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung Cancer. International journal of molecular sciences 65 27023518
2020 The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism. Nature structural & molecular biology 64 32572254
2020 Gating of human TRPV3 in a lipid bilayer. Nature structural & molecular biology 63 32572252
2011 SNP variants within the vanilloid TRPV1 and TRPV3 receptor genes are associated with migraine in the Spanish population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 63 22162417
2007 2-Aminoethoxydiphenyl borate as a common activator of TRPV1, TRPV2, and TRPV3 channels. Handbook of experimental pharmacology 61 17217057
2020 TRPV3 enhances skin keratinocyte proliferation through EGFR-dependent signaling pathways. Cell biology and toxicology 60 32535744
2013 TRPV3: a 'more than skinny' channel. Experimental dermatology 60 23800054
2013 TRPV3 channels mediate strontium-induced mouse-egg activation. Cell reports 60 24316078
2020 Enhanced Thermal Sensitivity of TRPV3 in Keratinocytes Underlies Heat-Induced Pruritogen Release and Pruritus in Atopic Dermatitis. The Journal of investigative dermatology 57 32247859
2020 Use of Epidermal Growth Factor Receptor Inhibitor Erlotinib to Treat Palmoplantar Keratoderma in Patients With Olmsted Syndrome Caused by TRPV3 Mutations. JAMA dermatology 56 31895432
2012 Intracellular proton-mediated activation of TRPV3 channels accounts for the exfoliation effect of α-hydroxyl acids on keratinocytes. The Journal of biological chemistry 56 22679014
2018 Pharmacological Inhibition of the Temperature-Sensitive and Ca2+-Permeable Transient Receptor Potential Vanilloid TRPV3 Channel by Natural Forsythoside B Attenuates Pruritus and Cytotoxicity of Keratinocytes. The Journal of pharmacology and experimental therapeutics 55 30377214
2016 TRPV3 in Drug Development. Pharmaceuticals (Basel, Switzerland) 55 27618069
2017 Single-residue molecular switch for high-temperature dependence of vanilloid receptor TRPV3. Proceedings of the National Academy of Sciences of the United States of America 54 28154143
2014 A new TRPV3 missense mutation in a patient with Olmsted syndrome and erythromelalgia. JAMA dermatology 53 24452206
2009 TRPV3, a thermosensitive channel is expressed in mouse distal colon epithelium. Biochemical and biophysical research communications 53 19336223
2009 A TR(I)P to pruritus research: role of TRPV3 in inflammation and itch. The Journal of investigative dermatology 50 19209153
2009 Monoterpenoids induce agonist-specific desensitization of transient receptor potential vanilloid-3 (TRPV3) ion channels. Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 50 19470296
2014 Acute heat-evoked temperature sensation is impaired but not abolished in mice lacking TRPV1 and TRPV3 channels. PloS one 49 24925072
2021 A plant-derived TRPV3 inhibitor suppresses pain and itch. British journal of pharmacology 48 33501656
2018 Antipruritic Effect of Natural Coumarin Osthole through Selective Inhibition of Thermosensitive TRPV3 Channel in the Skin. Molecular pharmacology 48 30108138
2007 Influence of TRPV3 mutation on hair growth cycle in mice. Biochemical and biophysical research communications 48 17888882
2019 Inhibition of the Warm Temperature-Activated Ca2+-Permeable Transient Receptor Potential Vanilloid TRPV3 Channel Attenuates Atopic Dermatitis. Molecular pharmacology 47 31308264
2013 Loss of interneuron LTD and attenuated pyramidal cell LTP in Trpv1 and Trpv3 KO mice. Hippocampus 46 23536486
2023 A pentameric TRPV3 channel with a dilated pore. Nature 45 37648856
2014 Thermally activated TRPV3 channels. Current topics in membranes 44 25366242
2021 Inhibition of temperature-sensitive TRPV3 channel by two natural isochlorogenic acid isomers for alleviation of dermatitis and chronic pruritus. Acta pharmaceutica Sinica. B 42 35256942
2017 TRPV3 Channel in Keratinocytes in Scars with Post-Burn Pruritus. International journal of molecular sciences 39 29140280
2012 Tonic inhibition of TRPV3 by Mg2+ in mouse epidermal keratinocytes. The Journal of investigative dermatology 39 22622423
2017 The Ca2+-Permeable Cation Transient Receptor Potential TRPV3 Channel: An Emerging Pivotal Target for Itch and Skin Diseases. Molecular pharmacology 38 28377424
2016 A novel mutation in TRPV3 gene causes atypical familial Olmsted syndrome. Scientific reports 38 26902751
2023 TRPV3: Structure, Diseases and Modulators. Molecules (Basel, Switzerland) 37 36677834
2020 Transient receptor potential vanilloid-3 (TRPV3) channel induces dermal fibrosis via the TRPV3/TSLP/Smad2/3 pathways in dermal fibroblasts. Journal of dermatological science 36 31959383
2014 TRPV3. Handbook of experimental pharmacology 36 24756710
2014 Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel. Journal of cell science 36 25413349
2021 Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine. eLife 35 33876725
2022 Structural basis of TRPV3 inhibition by an antagonist. Nature chemical biology 34 36302896
2017 A pivotal role for the activation of TRPV3 channel in itch sensations induced by the natural skin sensitizer carvacrol. Acta pharmacologica Sinica 33 29094727
2021 Hair Loss Caused by Gain-of-Function Mutant TRPV3 Is Associated with Premature Differentiation of Follicular Keratinocytes. The Journal of investigative dermatology 32 33675791
2020 Genotype‒Phenotype Correlation of TRPV3-Related Olmsted Syndrome. The Journal of investigative dermatology 32 32795529
2018 Activation of transient receptor potential vanilloid 3 channel (TRPV3) aggravated pathological cardiac hypertrophy via calcineurin/NFATc3 pathway in rats. Journal of cellular and molecular medicine 32 30299584
2009 Role of TRPV3 in immune response to development of dermatitis. Journal of inflammation (London, England) 31 19463197
2019 MiR-103 inhibiting cardiac hypertrophy through inactivation of myocardial cell autophagy via targeting TRPV3 channel in rat hearts. Journal of cellular and molecular medicine 30 30604587
2018 The bovine TRPV3 as a pathway for the uptake of Na+, Ca2+, and NH4+. PloS one 30 29494673
2013 Impact of TRPV3 on the development of allergic dermatitis as a dendritic cell modulator. Experimental dermatology 30 24164484
2024 TRPV3 activation by different agonists accompanied by lipid dissociation from the vanilloid site. Science advances 29 38691614
2017 Transient receptor potential vanilloid-3 (TRPV3) activation plays a central role in cardiac fibrosis induced by pressure overload in rats via TGF-β1 pathway. Naunyn-Schmiedeberg's archives of pharmacology 29 29249037
2021 MicroRNA-369 attenuates hypoxia-induced cardiomyocyte apoptosis and inflammation via targeting TRPV3. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 28 33470394
2019 Conserved allosteric pathways for activation of TRPV3 revealed through engineering vanilloid-sensitivity. eLife 27 30644819
2017 Effects of the Fruit Extract of Tribulus terrestris on Skin Inflammation in Mice with Oxazolone-Induced Atopic Dermatitis through Regulation of Calcium Channels, Orai-1 and TRPV3, and Mast Cell Activation. Evidence-based complementary and alternative medicine : eCAM 27 29348776
2015 TRPV3 channels mediate Ca²⁺ influx induced by 2-APB in mouse eggs. Cell calcium 27 26725171
2013 Cholesterol sensitises the transient receptor potential channel TRPV3 to lower temperatures and activator concentrations. Cell calcium 27 24406294
2023 TRPV3 Ion Channel: From Gene to Pharmacology. International journal of molecular sciences 26 37239947
2018 Strontium fails to induce Ca2+ release and activation in human oocytes despite the presence of functional TRPV3 channels. Human reproduction open 25 30895246
2022 Inhibition of intracellular proton-sensitive Ca2+-permeable TRPV3 channels protects against ischemic brain injury. Acta pharmaceutica Sinica. B 24 35646518
2022 TRPV3 and Itch: The Role of TRPV3 in Chronic Pruritus according to Clinical and Experimental Evidence. International journal of molecular sciences 24 36499288
2018 Activation of TRPV3 by Wood Smoke Particles and Roles in Pneumotoxicity. Chemical research in toxicology 24 29658714
2017 Marine Cyclic Guanidine Alkaloids Monanchomycalin B and Urupocidin A Act as Inhibitors of TRPV1, TRPV2 and TRPV3, but not TRPA1 Receptors. Marine drugs 24 28333079
2023 Involvement of skin TRPV3 in temperature detection regulated by TMEM79 in mice. Nature communications 23 37474531
2022 TRPV3 promotes the angiogenesis through HIF-1α-VEGF signaling pathway in A549 cells. Acta histochemica 23 36423389
2016 TRPV3 expression and vasodilator function in isolated uterine radial arteries from non-pregnant and pregnant rats. Vascular pharmacology 23 27073026
2016 TRPV3 mutants causing Olmsted Syndrome induce impaired cell adhesion and nonfunctional lysosomes. Channels (Austin, Tex.) 23 27754757
2013 Camphor modulates TRPV3 cation channels activity by interacting with critical pore-region cysteine residues. Pakistan journal of pharmaceutical sciences 23 23625413
2012 Supercooling agent icilin blocks a warmth-sensing ion channel TRPV3. TheScientificWorldJournal 23 22548000

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