Affinage

TRPM5

Transient receptor potential cation channel subfamily M member 5 · UniProt Q9NZQ8

Length
1165 aa
Mass
131.5 kDa
Annotated
2026-04-28
99 papers in source corpus 34 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRPM5 is a calcium-activated, voltage-modulated, monovalent-selective cation channel that transduces receptor-mediated intracellular Ca²⁺ signals into membrane depolarization across chemosensory, endocrine, and immune cell types. The channel is directly gated by rapid rises in intracellular Ca²⁺ (EC₅₀ ~0.7–21 µM depending on configuration), exhibits strong outward rectification due to voltage-sensitive gating, is impermeable to divalent cations, and desensitizes during sustained Ca²⁺ exposure; additional regulation is provided by temperature (heat shifts the voltage-activation curve), extracellular pH and Zn²⁺ (pore-loop block), PKC phosphorylation (synergistic activation at physiological voltages), and PIP₂ (PMID:12842017, PMID:14657398, PMID:16355226, PMID:23884414, PMID:38538847). In taste receptor cells, TRPM5 operates downstream of PLCβ2/IP₃-mediated Ca²⁺ release to generate the depolarization required for ATP secretion through pannexin 1 hemichannels, and Trpm5 knockout mice lose sweet, umami, and most bitter taste responses; TRPM4 functions in parallel, as double knockout abolishes all three modalities (PMID:16436689, PMID:20498227, PMID:29311301). Beyond gustation, TRPM5 sustains high-frequency Ca²⁺ oscillations in pancreatic β-cells required for glucose-induced insulin secretion, couples to Na⁺/Ca²⁺ exchange to drive mucin secretion in goblet cells, and negatively regulates Ca²⁺-dependent inflammatory signaling in B lymphocytes (PMID:20194741, PMID:23741618, PMID:32521253).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 High

    Establishing TRPM5 as the first voltage-modulated, Ca²⁺-activated monovalent cation channel resolved the ion-channel identity of the downstream depolarizing step in receptor-coupled taste signaling and defined its unique biophysical fingerprint (23 pS conductance, divalent-impermeable, outward rectification, rapid kinetics, Ca²⁺-rate sensitivity, PIP₂-reversible desensitization).

    Evidence Whole-cell and single-channel patch-clamp with Ca²⁺ uncaging, IP₃-pathway stimulation, and PIP₂ application in HEK293 cells, replicated across three independent laboratories

    PMID:12842017 PMID:14634208 PMID:14657398

    Open questions at the time
    • Ca²⁺-binding site residues not yet identified
    • structural basis of monovalent selectivity unknown
    • mechanism of desensitization not resolved
  2. 2005 High

    Demonstrating that TRPM5 is heat-activated via voltage-curve shifting and that extracellular acid blocks it through specific S3-S4 linker and pore residues established the physiological relevance of environmental modulators: temperature enhancement of sweet taste and acid modulation of taste perception.

    Evidence Patch-clamp at varied temperatures and pH in heterologous cells; site-directed mutagenesis of Glu (S3-S4) and His896 (pore); gustatory nerve recordings in WT vs Trpm5 KO mice

    PMID:15731110 PMID:16355226

    Open questions at the time
    • molecular identity of the temperature sensor domain not determined
    • physiological impact of acid block on in vivo taste coding not tested
  3. 2005 High

    Quantitative comparison with TRPM4 revealed ~30-fold higher Ca²⁺ sensitivity and insensitivity to ATP⁴⁻ block, distinguishing TRPM5 pharmacologically and physiologically from its closest paralog.

    Evidence Side-by-side whole-cell and inside-out patch-clamp with Ca²⁺ dialysis, UV uncaging, and ATP application in HEK293 cells

    PMID:15670874

    Open questions at the time
    • structural basis for differential Ca²⁺ sensitivity not resolved
    • in vivo functional redundancy between TRPM4 and TRPM5 not yet tested
  4. 2006 High

    Trpm5 knockout mice demonstrated that TRPM5 is essential for sweet, umami, and most bitter taste signaling in vivo, settling debate about its necessity in the taste transduction cascade.

    Evidence Chorda tympani and glossopharyngeal nerve recordings plus behavioral two-bottle preference tests in independently generated Trpm5-null mice

    PMID:16436689

    Open questions at the time
    • residual bitter taste in KO suggests TRPM5-independent pathways exist
    • TRPM4 contribution not yet addressed
  5. 2007 High

    Recording TRPM5 currents in native taste cells confirmed that IP₃/Ca²⁺ directly gates TRPM5 in its physiological context and revealed a second, distinct Ca²⁺-activated nonselective channel in taste cells.

    Evidence Whole-cell and excised patch-clamp in GFP-identified taste cells from TRPM5-promoter-GFP and Trpm5 KO mice with IP₃ uncaging

    PMID:17522321

    Open questions at the time
    • identity of the second Ca²⁺-activated channel unknown
    • relative contributions of the two channels to taste coding undefined
  6. 2010 High

    Showing that TRPM5-driven depolarization is required for taste-evoked ATP secretion through pannexin 1 hemichannels placed TRPM5 mechanistically between Ca²⁺ release and the neurotransmitter output step of type II taste cells.

    Evidence ATP biosensor assays on isolated vallate taste cells with pharmacological block and KO; rescue by KCl depolarization

    PMID:20498227

    Open questions at the time
    • precise voltage threshold for pannexin 1 opening not determined
    • whether TRPM5 and pannexin 1 form a complex is unknown
  7. 2010 High

    Extending TRPM5 function beyond taste, loss of Trpm5 in pancreatic β-cells abolished high-frequency Ca²⁺ oscillations and impaired glucose-induced insulin secretion and glucose tolerance, establishing TRPM5 as a component of the insulin secretory machinery.

    Evidence Ca²⁺ imaging and electrophysiology in isolated islets; insulin secretion assays; glucose and insulin tolerance tests in Trpm5 KO mice

    PMID:20194741 PMID:20393858

    Open questions at the time
    • precise position of TRPM5 within the β-cell oscillatory circuit not resolved
    • downstream coupling to exocytosis machinery unknown
  8. 2013 High

    Discovery that TRPM5-mediated Na⁺ influx drives Ca²⁺ entry via the Na⁺/Ca²⁺ exchanger to control mucin (MUC5AC) secretion in goblet cells revealed a non-chemosensory secretory function and an unexpected coupling between TRPM5 and NCX.

    Evidence Genome-wide siRNA screen followed by stable TRPM5 knockdown, patch-clamp, Ca²⁺ imaging, and NCX inhibition in HT29-18N2 goblet cells

    PMID:23741618

    Open questions at the time
    • whether TRPM5–NCX coupling operates in other secretory cell types is untested
    • post-Golgi granule fusion mechanism downstream of NCX-dependent Ca²⁺ not defined
  9. 2013 High

    Identification of pore-loop residues His896, Glu926, and Glu939 as the extracellular Zn²⁺ inhibition site provided the first molecular map of the TRPM5 outer pore selectivity filter region.

    Evidence Site-directed mutagenesis combined with whole-cell patch-clamp at varied Zn²⁺ concentrations

    PMID:23884414

    Open questions at the time
    • structural visualization of Zn²⁺ binding not available
    • physiological relevance of Zn²⁺ inhibition in vivo not tested
  10. 2014 Medium

    TRPM5 was found to mediate pheromone-evoked depolarization in a specialized subset of olfactory sensory neurons that lack ANO2 chloride channels and project to ventral olfactory bulb glomeruli processing semiochemicals, broadening TRPM5's chemosensory roles beyond taste.

    Evidence Ca²⁺ imaging, patch-clamp, and immunohistochemistry in GFP-identified TRPM5-expressing OSNs; glomerular mapping

    PMID:17267604 PMID:24573286

    Open questions at the time
    • behavioral consequence of TRPM5 loss specifically in OSNs not tested
    • whether TRPM5 is the sole depolarizing channel in these neurons not resolved
  11. 2018 High

    Genetic epistasis using TRPM4/TRPM5 double-knockout mice showed that TRPM4 and TRPM5 function in parallel to generate depolarization in taste cells, and that loss of both channels completely abolishes bitter, sweet, and umami detection.

    Evidence Live-cell Ca²⁺ imaging and behavioral assays in single and double KO mice

    PMID:29311301

    Open questions at the time
    • whether TRPM4 and TRPM5 form heteromeric channels is unknown
    • mechanism of their parallel contribution (same cells vs. different cells) not fully resolved
  12. 2019 Medium

    Mapping the shared Ca²⁺-binding site to S2-S3 residues in both TRPM4 and TRPM5 while revealing divergent PIP₂ sensitivity explained a long-standing puzzle: how channels with similar Ca²⁺ activation differ in desensitization recovery.

    Evidence Site-directed mutagenesis and inside-out/whole-cell patch-clamp with PIP₂ application in HEK293 cells

    PMID:31022885

    Open questions at the time
    • structural basis for differential PIP₂ sensitivity not determined
    • whether PIP₂ regulation differs in native taste cells unknown
  13. 2020 Medium

    Demonstrating that Trpm5-deficient B lymphocytes exhibit elevated cytosolic Ca²⁺, enhanced proliferation, and increased inflammatory cytokine production — with exacerbated endotoxic shock in vivo — established an immunomodulatory role in which TRPM5 negatively regulates Ca²⁺-dependent inflammatory signaling.

    Evidence Ca²⁺ imaging, cytokine ELISA, proliferation assays, and LPS-induced endotoxic shock model in Trpm5 KO mice

    PMID:32521253

    Open questions at the time
    • molecular mechanism of Ca²⁺ extrusion/dissipation by TRPM5 in B cells not defined
    • whether this role extends to other immune cell types not tested
  14. 2024 High

    Cryo-EM structures of TRPM5 in multiple Ca²⁺-bound states revealed that Ca²⁺-triggered formation and dissolution of cytoplasmic interprotomer interfaces control the activation-to-desensitization transition, providing the first structural framework for TRPM5 gating.

    Evidence Cryo-EM structural determination of rat TRPM5 combined with whole-cell patch-clamp electrophysiology

    PMID:38923985

    Open questions at the time
    • structures in the presence of PIP₂ or PKC-phosphorylated state not yet obtained
    • open-pore conduction state not captured
  15. 2024 Medium

    PKC phosphorylation was shown to synergize with Ca²⁺ for TRPM5 activation at physiological membrane potentials, resolving why physiological Ca²⁺ levels alone appeared insufficient to open the channel at resting voltages.

    Evidence Whole-cell patch-clamp with PKC activation/inhibition and Ca²⁺ manipulation in heterologous cells

    PMID:38538847

    Open questions at the time
    • phosphorylation site(s) on TRPM5 not identified
    • in vivo confirmation of PKC–TRPM5 synergy in taste or β-cells lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the specific PKC phosphorylation site(s), the structural basis for monovalent selectivity (computational predictions await experimental validation), whether TRPM4 and TRPM5 form heteromeric assemblies in native cells, and the full scope of TRPM5 function in tuft-cell-mediated innate immunity.
  • PKC phosphorylation site mapping needed
  • experimental validation of hydrophobic funnel selectivity model required
  • TRPM4/TRPM5 heteromer formation untested
  • tuft cell innate immune function only in preprint

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140299 molecular sensor activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-9709957 Sensory Perception 5 R-HSA-382551 Transport of small molecules 3 R-HSA-168256 Immune System 1
Partners
PANX1PLCΒ2SLC8A1TRPM4

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 TRPM5 forms a monovalent-selective cation channel (23 pS unitary conductance) that is directly activated by intracellular Ca2+ released via IP3-mediated pathways, displays voltage modulation with rapid activation/deactivation kinetics, and is impermeable to divalent cations; it was classified as the first voltage-modulated, Ca2+-activated monovalent cation channel (VCAM). Whole-cell and single-channel patch-clamp in HEK293 cells; receptor-stimulated activation via PLC-coupled pathway; Ca2+ uncaging Current Biology High 12842017 14634208 14657398
2003 TRPM5 is directly activated by micromolar intracellular Ca2+ (K1/2 ≈ 21 µM under whole-cell conditions) and shows strong outward rectification due to voltage-sensitive gating; sustained Ca2+ exposure causes desensitization, which is partially reversed by PIP2. Whole-cell patch-clamp with intracellular Ca2+ dialysis; inside-out patch with PIP2 application in heterologous expression system PNAS High 14634208 14657398 18537122
2003 TRPM5 responds specifically to the rate of change of intracellular Ca2+ rather than steady-state levels: rapid Ca2+ elevations generate large currents whereas slow elevations to identical concentrations are ineffective; the channel activates and deactivates transiently even during sustained Ca2+ elevation, producing a transient membrane depolarization. Whole-cell patch-clamp combined with Ca2+ imaging in HEK293 cells; IP3-producing agonist stimulation PNAS High 14634208
2005 TRPM5 is a heat-activated channel: inward currents increase steeply between 15 and 35°C due to a temperature-dependent shift of the voltage-activation curve, analogous to other thermosensitive TRP channels; heat activation of TRPM5 underlies temperature-dependent enhancement of sweet taste in vivo. Whole-cell patch-clamp at varied temperatures in heterologous system; gustatory nerve recordings in wild-type vs. Trpm5 knockout mice Nature High 16355226
2005 Compared to TRPM4, mouse TRPM5 has ~30-fold higher Ca2+ sensitivity (EC50 ≈ 0.7 µM vs. 20 µM for TRPM4 under whole-cell conditions); TRPM5 is insensitive to intracellular ATP4- at concentrations up to 1 mM, whereas TRPM4 is potently blocked by ATP4- (IC50 ≈ 0.8 µM); both channels are blocked equally by intracellular spermine. Whole-cell and inside-out patch-clamp; intracellular Ca2+ dialysis and UV uncaging; pharmacological comparison in HEK293 cells Cell Calcium High 15670874
2005 External acidification potently blocks TRPM5 currents (fast block IC50 pH 6.2) and also enhances irreversible current inactivation; a Glu residue in the S3-S4 linker and a His residue in the pore region (H896) are identified as key determinants of acid block, with double mutant showing near insensitivity (IC50 pH 5.0). Site-directed mutagenesis combined with whole-cell patch-clamp at varied extracellular pH in heterologous expression system Journal of Biological Chemistry High 15731110
2006 TRPM5 is required for normal sweet, umami, and bitter taste-evoked responses: Trpm5 knockout mice show absent or greatly reduced chorda tympani and glossopharyngeal nerve responses and behavioral preferences to sweet and umami compounds, with reduced (but not abolished) bitter avoidance, demonstrating TRPM5-dependent and TRPM5-independent taste pathways. Gustatory nerve recordings (chorda tympani and glossopharyngeal); licking behavior; 24-h two-bottle preference tests in Trpm5 null mice Chemical Senses High 16436689
2007 In native taste receptor cells, brief elevation of intracellular IP3 or Ca2+ is sufficient to gate TRPM5-dependent currents; in excised patches, only intracellular Ca2+ (half-activation at ~8 µM) activates TRPM5 directly, and the channel desensitizes with prolonged Ca2+ exposure; a second Ca2+-activated nonselective cation channel distinct from TRPM5 is also present in taste cells. Whole-cell and excised patch-clamp in GFP-identified taste cells from TRPM5-promoter-GFP mice and TRPM5 knockout mice; IP3 uncaging Journal of Neuroscience High 17522321
2007 TRPM5 inhibited by the bitter compound quinine (EC50 ≈ 50 µM) via decreased maximal TRPM5 conductance and accelerated channel closure; quinine suppresses sweet gustatory nerve responses in wild-type but not Trpm5 KO mice, establishing TRPM5 as a molecular locus for bitter-sweet taste interactions. Whole-cell patch-clamp in heterologous cells; gustatory nerve recordings and single-fiber analysis in wild-type vs. Trpm5 KO mice FASEB Journal High 18070821
2008 9-Phenanthrol inhibits human TRPM4 but not TRPM5, despite their structural similarity; the compound acts directly on TRPM4 in a voltage-independent manner with similar IC50 in whole-cell and inside-out configurations, indicating direct channel block without requirement for intracellular signaling. Whole-cell and inside-out patch-clamp in HEK293 cells stably transfected with human TRPM4 or TRPM5 British Journal of Pharmacology High 18297105
2010 TRPM5 is required for normal glucose-induced Ca2+ oscillation frequency in pancreatic beta-cells and for glucose-induced insulin secretion; Trpm5-/- islets lack high-frequency Ca2+ oscillations and show reduced insulin release, and Trpm5-/- mice exhibit impaired glucose tolerance. Ca2+ imaging and electrophysiology in isolated islets; glucose-induced insulin secretion assays; in vivo glucose tolerance tests in Trpm5 KO mice; immunofluorescence identification of TRPM5 in islets PNAS High 20194741
2010 TRPM5-dependent membrane depolarization in taste receptor (Type II) cells is required for taste-evoked ATP secretion through pannexin 1 hemichannels; TRPM5 KO cells show absent taste-evoked ATP release, but ATP release can be restored by direct KCl depolarization, indicating that TRPM5-driven membrane voltage (rather than Ca2+ alone) gates hemichannel opening. ATP biosensor assays on isolated vallate taste cells; pharmacological block of TRPM5; KO mice; extracellular ATP measurement Journal of Physiology High 20498227
2010 TRPM5 acts as an indispensable regulator of insulin secretion: Trpm5-/- mice show impaired glucose tolerance and reduced arginine-induced insulin secretion from isolated islets, while insulin sensitivity is normal, indicating a specific role for TRPM5 in the secretory machinery rather than in peripheral glucose utilization. In vivo glucose tolerance tests; insulin tolerance tests; static insulin secretion from isolated islets in Trpm5 KO mice Pflügers Archiv High 20393858
2011 TRPM5 mediates linoleic acid-induced membrane depolarization and CCK secretion from enteroendocrine STC-1 cells downstream of GPR120 and phospholipase C; siRNA knockdown of TRPM5 or GPR120 significantly reduces LA-induced TRPM5 currents, intracellular Ca2+ rise, and CCK release. siRNA knockdown; whole-cell patch-clamp; Ca2+ imaging; CCK ELISA in STC-1 cells American Journal of Physiology - Cell Physiology High 21998136
2013 TRPM5 mediates Na+ influx in human colon goblet cells (HT29-18N2), and this Na+ entry drives Ca2+ uptake via the Na+/Ca2+ exchanger (NCX), which is required for MUC5AC mucin secretion from post-Golgi secretory granules; TRPM5 knockdown reduces TRPM5-like current, ATP-induced Ca2+ signal, and MUC5AC secretion. siRNA screen (7343 genes); stable TRPM5 knockdown; patch-clamp; Ca2+ imaging; NCX inhibition; ELISA for MUC5AC in HT29-18N2 cells eLife High 23741618
2013 Extracellular Zn2+ inhibits TRPM5 activity (IC50 ≈ 4.3 µM at -80 mV) acting on the outer pore loop; His896, Glu926, and Glu939 in the pore loop are critical residues for Zn2+ inhibition, as their mutation impairs block. Whole-cell patch-clamp with extracellular ZnCl2 application; site-directed mutagenesis of pore loop residues in heterologous expression Journal of Biological Chemistry High 23884414
2014 N-linked glycosylation of TRPM5 occurs at a unique site, Asn932; abolishing this glycosylation (N932Q mutation) decreases TRPM5 current density without altering plasma membrane trafficking, indicating a functional rather than trafficking role for glycosylation. Mutagenesis (N932Q); SDS-PAGE; surface biotinylation; whole-cell patch-clamp; tunicamycin treatment in HEK293 cells Frontiers in Cellular Neuroscience Medium 24605085
2014 In main olfactory epithelium, TRPM5-expressing olfactory sensory neurons (OSNs) use a novel pheromone transduction pathway: pheromone stimulation opens CNG channels leading to Ca2+ entry that gates TRPM5 (instead of Cl- channels via ANO2 which is absent in these neurons), linking CNG channel activation to TRPM5-dependent depolarization. Ca2+ imaging; patch-clamp; immunohistochemistry for ANO2; GFP reporter mice for TRPM5-expressing OSNs; stimulation with putative pheromones and social odors Journal of Neuroscience Medium 24573286
2014 TRPM5 contributes importantly to the muscarinic receptor-dependent slow afterdepolarization (sADP) in layer 5 pyramidal neurons of mouse prefrontal cortex; the sADP requires a PLC signaling cascade and intracellular Ca2+, and is significantly reduced in Trpm5 KO mice. Whole-cell patch-clamp in brain slices; genetic KO; pharmacological PLC blockade Frontiers in Cellular Neuroscience Medium 25237295
2017 Steviol glycosides (stevioside, rebaudioside A) and their aglycon steviol potentiate TRPM5 activity; this potentiation enhances bitter, sweet, and umami taste perception and glucose-induced insulin secretion in a Trpm5-dependent manner; daily stevioside consumption prevents high-fat-diet-induced hyperglycemia in wild-type but not Trpm5-/- mice. Electrophysiology (TRPM5 current recording); behavioral taste assays; insulin secretion assays; in vivo metabolic tests in wild-type and Trpm5-/- mice Nature Communications High 28361903
2018 Both TRPM4 and TRPM5 are required for taste transduction: loss of either channel impairs taste-evoked signaling, and loss of both channels completely abolishes bitter, sweet, and umami detection in mice, demonstrating parallel/redundant roles of these two channels in taste receptor cells. Live cell Ca2+ imaging; behavioral studies in TRPM4 KO, TRPM5 KO, and TRPM4/TRPM5 double KO mice PNAS High 29311301
2019 TRPM4 and TRPM5 share the same Ca2+-binding site formed by negatively charged residues near/in the S2-S3 region; mutations of these residues reduce Ca2+ sensitivity similarly in both channels. However, PIP2 robustly recovers desensitized TRPM4 but has negligible effect on TRPM5, indicating divergent PIP2 regulation despite shared Ca2+-binding architecture. Site-directed mutagenesis; whole-cell and excised patch-clamp; intracellular PIP2 application in HEK293 cells International Journal of Molecular Sciences Medium 31022885
2020 TRPM5 negatively regulates Ca2+-dependent signaling in LPS-stimulated B lymphocytes: Trpm5-deficient B cells show elevated cytosolic Ca2+, enhanced proliferation, and increased production of inflammatory cytokines (IL-6, CXCL10); Trpm5-/- mice exhibit exacerbated endotoxic shock with high mortality. Ca2+ imaging; cytokine ELISA; proliferation assays; in vivo endotoxic shock model in Trpm5 KO mice Cell Reports Medium 32521253
2021 The pore helix of TRPM5 (residues L901, Y913, Q915, I916) is involved in voltage-dependent inactivation: alanine substitutions at Y913 and I916 increase the inactivation time constant, and glycine substitutions at L901, Y913, Q915, I916 reduce voltage-dependent inactivation, placing the outer pore loop as a structural determinant of this process. Site-directed mutagenesis; whole-cell patch-clamp at varied membrane potentials in heterologous expression Heliyon Medium 33553759
2022 TRPM5 binds the calcium-binding proteins calmodulin (CaM) and S100A1 at intracellular N-terminal regions; in vitro binding assays confirmed these interactions, and molecular docking/MD simulations identified common binding interface patterns involving basic residues. In vitro pull-down/binding assays; molecular docking; molecular dynamics simulations Biochemistry Low 35225608
2024 Cryo-EM structures of rat TRPM5 reveal that Ca2+ binding triggers a series of conformational transitions in which formation and dissolution of cytoplasmic interprotomer interfaces control channel activation and desensitization; Ca2+-dependent desensitization strongly alters channel activation. Cryo-EM structural determination; whole-cell patch-clamp electrophysiology PNAS High 38923985
2024 Monovalent selectivity of TRPM5 is mechanistically determined by a hydrophobic funnel at the entrance to the central channel cavity that permits monovalent but not divalent cations to enter; monovalent permeation proceeds by a cooperative knock-on mechanism between binding sites in the pore vestibule and central cavity; hydrophilic mutations in this transition zone abolish divalent exclusion. In silico electrophysiology (molecular dynamics simulations); mutagenesis informed by structural data Biophysical Journal Low 39086136
2024 PKC phosphorylation synergizes with intracellular Ca2+ elevation for TRPM5 activation: PKC phosphorylation is crucial for channel-evoked currents at physiological membrane potentials, while physiologically relevant Ca2+ levels alone only activate TRPM5 at positive voltages. Whole-cell patch-clamp; PKC inhibition/activation; intracellular Ca2+ manipulation in heterologous expression Communications Biology Medium 38538847
2006 Arachidonic acid activates TRPM5 at 10 µM in HEK293 cells; enzymes controlling intracellular arachidonic acid (MGL, COX-2, PLA2-IIA) are co-expressed with TRPM5 in taste bud cells, suggesting arachidonic acid as an endogenous lipid modulator of TRPM5 in taste signaling. Heterologous expression with arachidonic acid application and whole-cell patch-clamp; double-label immunofluorescence in taste tissue Biochimica et Biophysica Acta Low 16935556
2013 Insulin downregulates TRPM5 expression in pancreatic islets from leptin-deficient (db/db, ob/ob) diabetic mice; leptin treatment of ob/ob mice reverses the diabetic phenotype and upregulates Trpm5 expression; in MIN6 cells, insulin (but not glucose or leptin) dose-dependently downregulates TRPM5 expression. qPCR gene expression; Ca2+ oscillation imaging in islets; leptin/insulin treatment experiments in cell lines and in vivo Pflügers Archiv Medium 24221356
2025 In pancreatic beta-cells, beta-blockers paradoxically increase cAMP, which activates PKA to phosphorylate RYR2, triggering Ca2+-induced Ca2+ release (CICR) that then activates TRPM5, resulting in increased Ca2+ influx via voltage-dependent Ca2+ channels and enhanced glucose-stimulated insulin secretion. cAMP measurement; Ca2+ imaging; insulin secretion assays; PKA inhibition; in MIN6-K8 cells and isolated islets Pharmacology Research & Perspectives Medium 40222952
2014 TRPM5-expressing olfactory sensory neurons project axons primarily to ventral olfactory bulb glomeruli that process semiochemicals (urine, socially relevant signals), and TRPM5 channel activity mediates pheromone responses; these neurons coexpress the CNG channel subunit A2. Transgenic GFP reporter mice (TRPM5 promoter driving GFP); immunohistochemistry; glomerular activation mapping; Ca2+ imaging in identified OSN subpopulation Journal of Neuroscience Medium 17267604 24573286
2025 Tracheal tuft cells use TRPM5 to detect ATP released by pathogenic bacteria; Trpm5-dependent tuft cell activation drives leukotriene release, which recruits neutrophils and macrophages; Trpm5 KO mice fail to detect bacteria-released ATP and cannot clear Rodentibacter pneumotropicus infection. Trpm5 KO mice; in vivo infection models; leukotriene measurement; immune cell recruitment assays bioRxiv (preprint)preprint Medium bio_10.1101_2025.10.08.681191

Source papers

Stage 0 corpus · 99 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature 355 16355226
2003 Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proceedings of the National Academy of Sciences of the United States of America 345 14657398
2003 TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel. Current biology : CB 310 12842017
2003 TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i. Proceedings of the National Academy of Sciences of the United States of America 272 14634208
2006 Trpm5 null mice respond to bitter, sweet, and umami compounds. Chemical senses 249 16436689
2008 Murine intestinal cells expressing Trpm5 are mostly brush cells and express markers of neuronal and inflammatory cells. The Journal of comparative neurology 211 18537122
2005 Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice. Cell calcium 202 15670874
2007 TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells. BMC neuroscience 201 17610722
2010 Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice. Proceedings of the National Academy of Sciences of the United States of America 167 20194741
2007 The transduction channel TRPM5 is gated by intracellular calcium in taste cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 157 17522321
2008 9-phenanthrol inhibits human TRPM4 but not TRPM5 cationic channels. British journal of pharmacology 131 18297105
2017 Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. Nature communications 129 28361903
2007 Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals. Proceedings of the National Academy of Sciences of the United States of America 128 17267604
2017 Skn-1a/Pou2f3 functions as a master regulator to generate Trpm5-expressing chemosensory cells in mice. PloS one 126 29216297
2007 TRPM5-expressing solitary chemosensory cells respond to odorous irritants. Journal of neurophysiology 114 18160424
2018 TRPM4 and TRPM5 are both required for normal signaling in taste receptor cells. Proceedings of the National Academy of Sciences of the United States of America 112 29311301
2003 Mouse Tudor Repeat-1 (MTR-1) is a novel component of chromatoid bodies/nuages in male germ cells and forms a complex with snRNPs. Mechanisms of development 102 14550528
2000 Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression. Human molecular genetics 100 10607831
2010 TRPM5 regulates glucose-stimulated insulin secretion. Pflugers Archiv : European journal of physiology 94 20393858
2010 Intracellular Ca(2+) and TRPM5-mediated membrane depolarization produce ATP secretion from taste receptor cells. The Journal of physiology 78 20498227
2012 MTR1 encodes a secretory fasciclin glycoprotein required for male reproductive development in rice. Developmental cell 77 22698279
2011 The non-selective monovalent cationic channels TRPM4 and TRPM5. Advances in experimental medicine and biology 75 21290294
2003 Making sense with TRP channels: store-operated calcium entry and the ion channel Trpm5 in taste receptor cells. Cell calcium 74 12765699
2009 Release of endogenous opioids from duodenal enteroendocrine cells requires Trpm5. Gastroenterology 69 19272386
2007 The taste transduction channel TRPM5 is a locus for bitter-sweet taste interactions. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 68 18070821
2014 Skn-1a/Pou2f3 is required for the generation of Trpm5-expressing microvillous cells in the mouse main olfactory epithelium. BMC neuroscience 67 24428937
2007 TRPM5 and taste transduction. Handbook of experimental pharmacology 65 17217064
2008 TRPM5-expressing microvillous cells in the main olfactory epithelium. BMC neuroscience 61 19025635
2011 TRPM5 is critical for linoleic acid-induced CCK secretion from the enteroendocrine cell line, STC-1. American journal of physiology. Cell physiology 60 21998136
2008 Is TrpM5 a reliable marker for chemosensory cells? Multiple types of microvillous cells in the main olfactory epithelium of mice. BMC neuroscience 52 19055837
2012 The role of T1r3 and Trpm5 in carbohydrate-induced obesity in mice. Physiology & behavior 50 22683548
2005 Extracellular acid block and acid-enhanced inactivation of the Ca2+-activated cation channel TRPM5 involve residues in the S3-S4 and S5-S6 extracellular domains. The Journal of biological chemistry 50 15731110
2006 Arachidonic acid can function as a signaling modulator by activating the TRPM5 cation channel in taste receptor cells. Biochimica et biophysica acta 47 16935556
2017 TRPM5 in the battle against diabetes and obesity. Acta physiologica (Oxford, England) 42 28834354
2013 TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells. eLife 41 23741618
2017 TRPM5 mediates acidic extracellular pH signaling and TRPM5 inhibition reduces spontaneous metastasis in mouse B16-BL6 melanoma cells. Oncotarget 40 29108231
2013 Impact of T1r3 and Trpm5 on carbohydrate preference and acceptance in C57BL/6 mice. Chemical senses 40 23547138
2022 Circadian rhythm modulates endochondral bone formation via MTR1/AMPKβ1/BMAL1 signaling axis. Cell death and differentiation 39 35094018
2012 Second-order input to the medial amygdala from olfactory sensory neurons expressing the transduction channel TRPM5. The Journal of comparative neurology 37 22120520
2011 Genetic variation within the TRPM5 locus associates with prediabetic phenotypes in subjects at increased risk for type 2 diabetes. Metabolism: clinical and experimental 36 21489577
2009 Sensory attributes of complex tasting divalent salts are mediated by TRPM5 and TRPV1 channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 19244541
2014 Glycosylation of TRPM4 and TRPM5 channels: molecular determinants and functional aspects. Frontiers in cellular neuroscience 34 24605085
2000 Mtr1, a novel biallelically expressed gene in the center of the mouse distal chromosome 7 imprinting cluster, is a member of the Trp gene family. Genomics 34 10903843
2014 Differential contribution of TRPM4 and TRPM5 nonselective cation channels to the slow afterdepolarization in mouse prefrontal cortex neurons. Frontiers in cellular neuroscience 33 25237295
2022 Structure and mechanism of the methyltransferase ribozyme MTR1. Nature chemical biology 32 35301481
2014 Transduction for pheromones in the main olfactory epithelium is mediated by the Ca2+ -activated channel TRPM5. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 24573286
2015 A Binary Genetic Approach to Characterize TRPM5 Cells in Mice. Chemical senses 31 25940069
2017 Lack of TRPM5-Expressing Microvillous Cells in Mouse Main Olfactory Epithelium Leads to Impaired Odor-Evoked Responses and Olfactory-Guided Behavior in a Challenging Chemical Environment. eNeuro 29 28612045
2014 TRPM5. Handbook of experimental pharmacology 29 24756718
2014 Differential effects of bitter compounds on the taste transduction channels TRPM5 and IP3 receptor type 3. Chemical senses 28 24452633
2018 ATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epithelium. Frontiers in cellular neuroscience 27 29615870
1987 A 5-methyltryptophan resistant rice mutant, MTR1, selected in tissue culture. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 27 24241455
2015 Ablation of TRPM5 in Mice Results in Reduced Body Weight Gain and Improved Glucose Tolerance and Protects from Excessive Consumption of Sweet Palatable Food when Fed High Caloric Diets. PloS one 26 26397098
2010 The T1R2/T1R3 sweet receptor and TRPM5 ion channel taste targets with therapeutic potential. Progress in molecular biology and translational science 24 20691962
2008 Quantitative assessment of TRPM5-dependent oral aversiveness of pharmaceuticals using a mouse brief-access taste aversion assay. Behavioural pharmacology 24 18797244
2013 Insulin downregulates the expression of the Ca2+-activated nonselective cation channel TRPM5 in pancreatic islets from leptin-deficient mouse models. Pflugers Archiv : European journal of physiology 22 24221356
2021 Transcriptional profiling reveals potential involvement of microvillous TRPM5-expressing cells in viral infection of the olfactory epithelium. BMC genomics 19 33781205
2013 Extracellular zinc ion regulates transient receptor potential melastatin 5 (TRPM5) channel activation through its interaction with a pore loop domain. The Journal of biological chemistry 19 23884414
2017 Trpm5 expression in the olfactory epithelium. Molecular and cellular neurosciences 18 28188885
2020 Residual Glucose Taste in T1R3 Knockout but not TRPM5 Knockout Mice. Physiology & behavior 17 32417232
2019 TRPM4 and TRPM5 Channels Share Crucial Amino Acid Residues for Ca2+ Sensitivity but Not Significance of PI(4,5)P2. International journal of molecular sciences 17 31022885
2020 Activation of the bitter taste sensor TRPM5 prevents high salt-induced cardiovascular dysfunction. Science China. Life sciences 16 32303962
2020 TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes. Cell reports 16 32521253
2024 Sodium-Permeable Ion Channels TRPM4 and TRPM5 are Functional in Human Gastric Parietal Cells in Culture and Modulate the Cellular Response to Bitter-Tasting Food Constituents. Journal of agricultural and food chemistry 14 38378185
2023 Catalytic mechanism and pH dependence of a methyltransferase ribozyme (MTR1) from computational enzymology. Nucleic acids research 14 37070188
2014 Flavor preference conditioning by different sugars in sweet ageusic Trpm5 knockout mice. Physiology & behavior 14 25497884
2011 A conditioned aversion study of sucrose and SC45647 taste in TRPM5 knockout mice. Chemical senses 14 21987728
2013 TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response. American journal of physiology. Gastrointestinal and liver physiology 13 23639808
2018 Nicotinic acetylcholine receptors (nAChRs) are expressed in Trpm5 positive taste receptor cells (TRCs). PloS one 11 29293602
2020 TRPM5-expressing Microvillous Cells Regulate Region-specific Cell Proliferation and Apoptosis During Chemical Exposure. Neuroscience 10 32224228
2020 Transcriptional profiling reveals potential involvement of microvillous TRPM5-expressing cells in viral infection of the olfactory epithelium. bioRxiv : the preprint server for biology 10 32511400
2024 TRPM3, TRPM4, and TRPM5 as thermo-sensitive channels. The journal of physiological sciences : JPS 9 39294615
2022 Dietary experience with glucose and fructose fosters heightened avidity for glucose-containing sugars independent of TRPM5 taste transduction in mice. Nutritional neuroscience 9 35311614
2021 Identification of positive modulators of TRPM5 channel from a high-throughput screen using a fluorescent membrane potential assay. SLAS discovery : advancing life sciences R & D 7 35058176
2020 l-Glutamate stimulates cholecystokinin secretion via the T1R1/T1R3 mediated PLC/TRPM5 transduction pathway. Journal of the science of food and agriculture 7 32478409
2025 Loss of β-Cell KATP Reduces Ca2+ Sensitivity of Insulin Secretion and Trpm5 Expression. Diabetes 6 39666394
2024 Structural dynamics at cytosolic interprotomer interfaces control gating of a mammalian TRPM5 channel. Proceedings of the National Academy of Sciences of the United States of America 5 38923985
2022 TRPM5 Channel Binds Calcium-Binding Proteins Calmodulin and S100A1. Biochemistry 5 35225608
2018 Chemical Exposure-Induced Changes in the Expression of Neurotrophins and Their Receptors in the Main Olfactory System of Mice Lacking TRPM5-Expressing Microvillous Cells. International journal of molecular sciences 5 30261693
2010 Adding efficiency: the role of the CAN ion channels TRPM4 and TRPM5 in pancreatic islets. Islets 5 21099334
2021 TAS1R2 rs35874116 and TRPM5 rs886277 polymorphisms are not related with risk of obesity. International journal of clinical practice 4 34157195
2014 Differential localization of NT-3 and TrpM5 in glomeruli of the olfactory bulb of mice. The Journal of comparative neurology 4 24288162
2025 β-Adrenergic Blockers Increase cAMP and Stimulate Insulin Secretion Through a PKA/RYR2/TRPM5 Pathway in Pancreatic β-Cells In Vitro. Pharmacology research & perspectives 3 40222952
2025 The TRPM5 Antagonist Triphenylphosphine Oxide Increases Sebaceous Lipogenesis and Modulates Immune Phenotype of Human Sebocytes in a TRPM5-Independent Manner. Experimental dermatology 3 40329688
2018 The role of the transient receptor potential melastatin5 (TRPM5) channels in the pancreatic β-cell electrical activity: A computational modeling study. Computational biology and chemistry 3 29982164
2024 TRPM5 activation depends on a synergistic effect of calcium and PKC phosphorylation. Communications biology 2 38538847
2022 The discovery of (1R, 3R)-1-(3-chloro-5-fluorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonitrile, a potent and selective agonist of human transient receptor potential cation channel subfamily m member 5 (TRPM5) and evaluation of as a potential gastrointestinal prokinetic agent. Bioorganic & medicinal chemistry 2 36402081
2021 TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients. Journal of clinical medicine 2 33525598
2021 Association of TRPM5 Asn235Ser Polymorphism and Trace Elements/Minerals in Chronic Gastritis Patients: a Case-Control Study. Biological trace element research 2 34767145
2025 Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis. Journal of translational medicine 1 39863860
2024 Insufficient TRPM5 Mediates Lipotoxicity-induced Pancreatic β-cell Dysfunction. Current medical science 1 38517672
2024 A hydrophobic funnel governs monovalent cation selectivity in the ion channel TRPM5. Biophysical journal 1 39086136
2021 Involvement of pore helix in voltage-dependent inactivation of TRPM5 channel. Heliyon 1 33553759
2026 Immunohistochemical profiling of small cell lung cancer reveals subtype heterogeneity and a tuft cell-like subtype characterized by LRMP and TRPM5. Virchows Archiv : an international journal of pathology 0 41739157
2026 Enhancement of stevioside by abiotic elicitation in Stevia rebaudiana and upregulation of INS1, TRPM5, and GLP-1 in β-cells via plant extracts. Natural product research 0 42048544
2025 Identification of potent antibacterial inhibitors targeting methyltransferase Mtr1/TrmD in Haemophilus influenzae via molecular dynamics simulations. PloS one 0 40875735
2025 Deoxynivalenol-induced anorexia is mediated by brain-gut peptides through CaSR-TRPM5 signaling axis. Toxicon : official journal of the International Society on Toxinology 0 41241198
2025 Estrogen Dependent Variation in the Contributions of TRPM4 and TRPM5 to Fat Taste. bioRxiv : the preprint server for biology 0 41278770
2025 Estrogen-Dependent Variation in the Contributions of TRPM4 and TRPM5 to Fat Taste. Nutrients 0 41470794