Affinage

TRPM1

Transient receptor potential cation channel subfamily M member 1 · UniProt Q7Z4N2

Length
1603 aa
Mass
182.2 kDa
Annotated
2026-04-28
88 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRPM1 is a constitutively active, Ca²⁺-permeable nonselective cation channel that serves as the transduction channel in retinal ON-bipolar cells and regulates Ca²⁺-dependent melanogenesis in melanocytes. In ON-bipolar cells, TRPM1 localizes to dendritic tips via a transsynaptic organizing complex requiring presynaptic LRIT3, postsynaptic nyctalopin, and mGluR6; the mGluR6/Gαo cascade closes the channel in darkness through cooperative action of both Gβγ and Gαo subunits, while light-evoked glutamate reduction permits constitutive channel opening and cell depolarization (PMID:19861548, PMID:22586107, PMID:26883481, PMID:31189098). Cryo-EM reveals a tetrameric architecture with an unprecedented inverted transmembrane domain topology—clockwise domain-swapped pore modules with a dilated selectivity filter and wide intracellular gate—consistent with its constitutive open state (PMID:41857038). In melanocytes, TRPM1 mediates Ca²⁺ influx coupled positively (rather than negatively) to mGluR6 owing to the absence of Gαo, thereby promoting tyrosinase activity and melanin synthesis; TRPM1 is also the autoantigen in melanoma-associated retinopathy, where patient autoantibodies enter ON-bipolar cells and cause functional impairment and degeneration (PMID:23452348, PMID:21411639, PMID:24282602).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2004 Medium

    MITF was identified as a direct transcriptional activator of TRPM1 in melanocytes, establishing how TRPM1 expression is coupled to the melanocyte differentiation program.

    Evidence Promoter-luciferase deletion analysis identified two E-box elements required for MITF-driven TRPM1 transcription in melanoma cells.

    PMID:15577322

    Open questions at the time
    • No chromatin-level (ChIP) validation of MITF occupancy
    • Regulation in retinal ON-bipolar cells not addressed
  2. 2009 High

    Three independent studies established TRPM1 as the transduction channel of retinal ON-bipolar cells and a Ca²⁺-conducting channel in melanocytes, resolving the molecular identity of the ON pathway channel that had been sought for decades.

    Evidence TRPM1⁻/⁻ mice lacked ERG b-waves and ON-bipolar cell light responses; TRPM1 colocalized with mGluR6 at dendritic tips; constitutive channel activity was demonstrated in heterologous cells and inhibited by Gαo; TRPM1 current was recorded in melanocytes and abolished by miRNA knockdown [PMID:19861548, PMID:19966281, PMID:19436059].

    PMID:19436059 PMID:19587221 PMID:19861548 PMID:19966281

    Open questions at the time
    • Gating mechanism (Gα vs Gβγ) unresolved
    • Subunit stoichiometry unknown
    • Mechanism of dendritic tip targeting unclear
  3. 2011 High

    A macromolecular signaling complex was defined at ON-bipolar cell dendritic tips: nyctalopin scaffolds TRPM1 and mGluR6, mGluR6 is required for TRPM1 trafficking to dendritic tips, and PKCα modulates TRPM1 by relieving Mg²⁺-dependent inhibition—establishing the postsynaptic architecture and a gain-control mechanism.

    Evidence Proteomic/Co-IP identified nyctalopin–TRPM1 and nyctalopin–mGluR6 complexes; mGluR6⁻/⁻ mice showed loss of TRPM1 dendritic tip localization and inactive channels; PKCα activation via DAG relieved intracellular Mg²⁺ block of TRPM1 current in rod bipolar cells [PMID:21832182, PMID:22131384, PMID:21940450].

    PMID:21832182 PMID:21940450 PMID:22131384

    Open questions at the time
    • Direct binding interface between nyctalopin and TRPM1 not mapped
    • Mechanism by which PKCα relieves Mg²⁺ block at the channel level unknown
  4. 2011 High

    TRPM1 was identified as the autoantigen in melanoma-associated retinopathy (MAR), and its biophysical properties—including zinc inhibition and pore-region determinants—were characterized, establishing a disease mechanism and channel pharmacology.

    Evidence MAR sera specifically labeled TRPM1-transfected cells and WT but not TRPM1⁻/⁻ retina; extracellular zinc inhibited TRPM1 via a 7-amino-acid pore sequence; TRPM1/TRPM3 heteromultimeric channels were reconstituted [PMID:21411639, PMID:21278253].

    PMID:21278253 PMID:21411639

    Open questions at the time
    • Mechanism of autoantibody internalization into bipolar cells not resolved
    • Physiological relevance of zinc modulation in vivo unclear
  5. 2012 High

    Gβγ was identified as the direct inhibitory subunit that closes TRPM1, and a pore-domain dominant-negative mutation (A1068T) showed that the number of functional channel complexes at dendritic tips determines ON-bipolar cell response amplitude.

    Evidence Dialysis of purified Gβγ (but not Gαo) closed TRPM1 in bipolar cells, melanocytes, and HEK293 cells; heterozygous Trpm1-A1068T mice had reduced b-waves proportional to loss of functional channels [PMID:22586107, PMID:22896717].

    PMID:22586107 PMID:22896717

    Open questions at the time
    • Binding site of Gβγ on TRPM1 not structurally resolved
    • Whether A1068T disrupts pore gating or assembly not distinguished
  6. 2013 High

    The coupling polarity between mGluR6 and TRPM1 was shown to be cell-type-dependent: negative in retina (via Gαo) and positive in melanocytes (which lack Gαo), explaining how the same receptor–channel pair produces opposite functional outcomes in different tissues.

    Evidence Knockdown of TRPM1 or mGluR6 in melanocytes abolished L-AP4-induced Ca²⁺ influx; forced Gαo expression in melanocytes restored negative coupling as seen in retina [PMID:23452348].

    PMID:23452348

    Open questions at the time
    • Identity of the G-protein subunit mediating positive coupling in melanocytes not established
    • Whether additional signaling intermediaries participate is unknown
  7. 2013 High

    MAR autoantibodies were shown to be pathogenic in vivo: intravitreal injection caused ON-bipolar cell apoptosis and persistent ERG b-wave reduction, dependent on TRPM1 expression, establishing a direct autoimmune mechanism.

    Evidence Purified MAR IgG injected intravitreally reduced b-wave and caused TUNEL-positive bipolar cell death in WT but not TRPM1⁻/⁻ mice [PMID:24282602, PMID:23936334].

    PMID:23936334 PMID:24282602

    Open questions at the time
    • Mechanism of antibody-induced cell death (channel block vs complement vs signaling) not determined
  8. 2016 High

    The initial model of Gβγ-only gating was revised: both Gαo and Gβγ cooperate to close TRPM1, with BRET mapping showing Gαo binds both N- and C-termini while Gβγ binds only the N-terminus, providing a dual-subunit gating model.

    Evidence Constitutively active Gαo closed TRPM1 after light activation; phosducin (sequestering Gβγ) opened channels in darkness; BRET and Co-IP mapped subunit-specific interaction domains [PMID:26883481].

    PMID:26883481

    Open questions at the time
    • Structural basis of dual-subunit gating not resolved
    • Relative contribution of each subunit to gating kinetics unknown
  9. 2017 High

    TRPM1 channel activity was shown to be required for postnatal rod bipolar cell development and synaptogenesis with AII amacrine cells, extending TRPM1's role beyond signal transduction to circuit maturation.

    Evidence TRPM1⁻/⁻ mice had contracted rod bipolar terminals and fewer synapses; Channelrhodopsin-2 overexpression partially rescued development [PMID:28899920].

    PMID:28899920

    Open questions at the time
    • Whether the developmental role reflects Ca²⁺ signaling or depolarization per se is unresolved
    • Downstream transcriptional programs not identified
  10. 2019 High

    LRIT3 was revealed to act as a presynaptic transsynaptic organizer that directs postsynaptic assembly of the TRPM1-containing signalplex, resolving how the dendritic tip complex is organized across the synapse.

    Evidence AAV-mediated LRIT3 restoration specifically in Lrit3⁻/⁻ rods (not bipolar cells) rescued TRPM1 localization and rod-driven ERG responses [PMID:31189098].

    PMID:31189098

    Open questions at the time
    • Postsynaptic receptor for LRIT3 not identified
    • Whether LRIT3 directly contacts TRPM1 or acts via nyctalopin/mGluR6 is unresolved
  11. 2026 High

    The cryo-EM structure of TRPM1 revealed an unprecedented inverted transmembrane topology with clockwise domain-swapped pore modules, a dilated selectivity filter, and a wide intracellular gate, providing a structural basis for constitutive activity and distinguishing TRPM1 from all other structurally characterized TRP channels.

    Evidence Two independent cryo-EM studies resolved the TRPM1 tetramer, confirmed by single-channel electrophysiology showing constitutive openings [PMID:41857038].

    PMID:41857038

    Open questions at the time
    • Structure of TRPM1 in complex with Gαo or Gβγ not determined
    • Mechanism by which G-protein binding induces channel closure not structurally resolved
    • No structure with nyctalopin or mGluR6 complex partners

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of G-protein–mediated channel closure, the identity of the postsynaptic receptor for presynaptic LRIT3, the mechanism by which MAR autoantibodies cause bipolar cell death, and whether TRPM1's role in extra-retinal tissues (amygdala, iris) involves the same signaling complex as in ON-bipolar cells.
  • No TRPM1–G-protein co-structure available
  • Transsynaptic binding partner of LRIT3 on the postsynaptic side unidentified
  • Pathogenic mechanism of MAR autoantibodies at the molecular level unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 8
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-9709957 Sensory Perception 6 R-HSA-162582 Signal Transduction 5
Partners
GNAO1GNB3GRM6LRIT3NYXPRKCAS100A1TRPM3
Complex memberships
TRPM1-Gαo-Gβ3γ13 complexmGluR6-TRPM1-nyctalopin signalplex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 TRPM1 is necessary for the depolarizing light response of retinal ON-bipolar cells and is a component of the cation channel that generates this response, as demonstrated by loss of the ERG b-wave and abolition of chemically simulated light responses in patch-clamp recordings from TRPM1-/- mice. ERG recordings, whole-cell patch-clamp in retinal slices, TRPM1-/- knockout mice, in situ hybridization, immunofluorescence confocal microscopy Proceedings of the National Academy of Sciences of the United States of America High 19861548
2009 TRPM1 long form (TRPM1-L) is localized to dendritic tips of ON bipolar cells colocalizing with mGluR6, functions as a constitutively active nonselective cation channel, and its activity is negatively regulated by Go in the mGluR6 cascade; TRPM1 null mice completely lose the photoresponse of ON BCs. Immunofluorescence localization, TRPM1-/- knockout mice, ERG, electrophysiology in TRPM1-L-expressing cells, Go regulation assay Proceedings of the National Academy of Sciences of the United States of America High 19966281
2009 TRPM1 forms ion channels in melanocytes; endogenous TRPM1 current in human neonatal epidermal melanocytes and mouse melanoma cells was abrogated by miRNA directed against TRPM1, and TRPM1 is predominantly found in intracellular vesicular structures with small plasma membrane currents. Electrophysiology (patch-clamp), miRNA knockdown, subcellular localization imaging Science signaling High 19436059
2009 TRPM1 knockdown in human melanocytes reduces intracellular Ca2+ and Ca2+ uptake, decreases tyrosinase activity and melanin pigment; p53 induction (by transfection or UVB) represses TRPM1 expression, demonstrating TRPM1's role in Ca2+ homeostasis and melanogenesis. Lentiviral shRNA knockdown, Ca2+ imaging/measurement, tyrosinase activity assay, p53 transfection, UVB irradiation American journal of physiology. Cell physiology Medium 19587221
2011 TRPM1 forms a complex with nyctalopin in mouse retina (identified by proteomic search/Co-IP); nyctalopin also interacts with mGluR6; disruption of mGluR6 prevented targeting of TRPM1 to the postsynaptic compartment of ON-bipolar neurons, revealing a macromolecular signaling complex scaffolded by nyctalopin. Proteomic search, Co-immunoprecipitation, immunofluorescence, mGluR6-/- mice The Journal of neuroscience : the official journal of the Society for Neuroscience High 21832182
2011 TRPM1 is an ion-conducting plasma membrane channel inhibited by extracellular zinc ions at physiological concentrations; the zinc inhibition is due to a short stretch of seven amino acids unique to the pore region of TRPM1 but not TRPM3; unmodified TRPM1 and TRPM3 form functional heteromultimeric channels. Heterologous expression, patch-clamp electrophysiology, steroid activation, site-directed mutagenesis of pore region, TRPM1/TRPM3 heteromultimer reconstitution The Journal of biological chemistry High 21278253
2012 G-protein-mediated inhibition of TRPM1 in ON-bipolar cells requires the Gβγ dimer, not Gαo: dialysis of Gβγ (but not Gαo) closed TRPM1 channels in retinal bipolar cells, melanocytes, and HEK293 cells; activation of an endogenous GPCR pathway releasing Gβγ without activating Go also closed TRPM1. Patch-clamp electrophysiology (intracellular dialysis of protein subunits), multiple cell types including native bipolar cells and heterologous systems Proceedings of the National Academy of Sciences of the United States of America High 22586107
2011 TRPM1 localized at the ultrastructural level to the tips of ON-bipolar cell dendrites invaginating cone pedicles and rod spherules in human retina; additionally TRPM1 immunoreactivity was found on synaptic ribbons of a subclass of rods, suggesting a dual function in the ON pathway. Electron microscopy immunohistochemistry, in situ hybridization, laser dissection microscopy/PCR Investigative ophthalmology & visual science Medium 21896854
2011 Deletion of mGluR6 renders TRPM1 channels inactive in rod bipolar cells; mGluR6 null mice show hyperpolarized rod bipolar cells with reduced slope conductance and current noise; TRPM1 immunostaining at dendritic tips is greatly reduced without mGluR6, indicating mGluR6-dependent postsynaptic targeting of TRPM1. Whole-cell patch-clamp, capsaicin application, immunostaining in mGluR6-/- mice Journal of neurophysiology High 22131384
2011 Autoantibodies in melanoma-associated retinopathy (MAR) target TRPM1 in retinal ON-bipolar cells; MAR sera stain TRPM1-transfected HEK cells and ON-bipolar cells in TRPM1+/+ but not TRPM1-/- retina; the autoantibody epitope is likely intracellular and antibodies can be internalized by retinal cells. Immunofluorescence on TRPM1-transfected HEK cells and TRPM1-/- mouse retina, Western blot, confocal colocalization The Journal of neuroscience : the official journal of the Society for Neuroscience High 21411639
2011 TRPM1 current in rod bipolar cells is susceptible to voltage-independent inhibition by intracellular magnesium; PKCα activation (via DAG/OAG) relieves this Mg2+ inhibition and potentiates TRPM1 current specifically in rod but not cone ON-bipolar cells, dependent on PIP2 hydrolysis. Whole-cell patch-clamp, DAG analog (OAG) application, PKCα knockout mice, pharmacological inhibition, PIP2 hydrolysis manipulation The Journal of neuroscience : the official journal of the Society for Neuroscience High 21940450
2004 TRPM1 expression in melanocytes and melanoma is regulated by the transcription factor MITF via a 654 bp upstream sequence containing four E boxes (including an M box); deletion analysis showed that two distal E boxes (E3 and E4) are required for MITF activation and constitutive activity in melanoma. Promoter-luciferase reporter assay, deletion analysis, Western blot Melanoma research Medium 15577322
2013 Human melanocytes express mGluR6, and mGluR6 signaling positively couples to TRPM1 in melanocytes (opposite to the negative coupling in retina); knockdown of TRPM1 or mGluR6 abolished L-AP4-induced Ca2+ influx; forced Gαo expression restored negative coupling; absence of Gαo explains the different coupling polarity in melanocytes versus retina. shRNA knockdown, Ca2+ imaging, patch-clamp electrophysiology, Gαo overexpression, pertussis toxin treatment Pigment cell & melanoma research High 23452348
2013 Serum TRPM1 autoantibodies from MAR patients enter retinal ON-bipolar cells after intravitreal injection and attenuate the ERG b-wave in wild-type but not TRPM1-/- mice; the autoantibody epitope is within the amino-terminal cytoplasmic domain of TRPM1. Intravitreal injection of MAR IgG, ERG recording, immunofluorescence on TRPM1+/+ and TRPM1-/- retinas, TRPM1-transfected CHO cell labeling PloS one High 23936334
2014 Purified recombinant TRPM1 is mostly dimeric (not tetrameric) as determined by blue native gels, size exclusion chromatography, cross-linking, and cryo-EM single-particle analysis; native retinal TRPM1 exists in two complexes of distinct sizes, suggesting additional partner subunits participate in the functional transduction channel. Recombinant protein purification from insect cells, blue native PAGE, size exclusion chromatography, cross-linking, cryo-EM single-particle analysis, antibody-TRPM1 complex EM The Journal of biological chemistry Medium 25112866
2015 LRIT3 is essential for localizing TRPM1 to the dendritic tips of depolarizing bipolar cells; in Lrit3-/- mice, TRPM1 staining is severely decreased at dendritic tips of all depolarizing bipolar cells. Immunofluorescence confocal microscopy in Lrit3-/- mice versus wild-type The European journal of neuroscience Medium 25997951
2016 Both the α (Gαo) and βγ (Gβγ) subunits of Go gate TRPM1 in ON-bipolar cells: a constitutively active Gαo mutant closed TRPM1 channels after light activation; phosducin or inactive Gαo (sequestering Gβγ) opened channels in darkness; Co-IP showed TRPM1 interacts with Gβ3 and both active and inactive Gαo; BRET assays showed Gαo interacts with both N- and C-termini of TRPM1 while Gβγ interacts only with the N-terminus. Intracellular dialysis patch-clamp in rod bipolar cells, Co-immunoprecipitation, bioluminescent energy transfer (BRET) Scientific reports High 26883481
2015 Voriconazole inhibits TRPM1 channels in retinal ON-bipolar cells; patch-clamp recording showed voriconazole blocks capsaicin-activated TRPM1 currents in ON-bipolar cells and TRPM3 currents in transfected CHO cells, while only slightly inhibiting mGluR6-mediated GIRK currents. ERG recordings, whole-cell patch-clamp in retinal slices and transfected CHO cells Investigative ophthalmology & visual science Medium 25650413
2015 PIP2 binds to an N-terminal fragment of TRPM1 (residues A451-N566); the basic residue K464 is part of a putative pleckstrin homology domain involved in PIP2 interaction, characterized by biophysical methods and molecular modeling. Biophysical binding assays, molecular modeling, mutagenesis of K464 Biophysical chemistry Low 26544986
2016 S100A1 binds to the N-terminal L242-E344 region of TRPM1 in a calcium-dependent manner; complex formation requires clusters of positively charged (K271, R273, R274) and hydrophobic (L263, V270, L276) residues, characterized by fluorescence spectroscopy and mutagenesis. Fluorescence spectroscopy, bioinformatics/structural modeling, mutagenesis The international journal of biochemistry & cell biology Low 27435061
2018 The majority of TRPM1 in retinal ON-bipolar cells resides in the endoplasmic reticulum (ER), not at the plasma membrane; in heterologous cells, recombinant TRPM1 colocalizes with ER markers; fluorescence protease protection assays showed both N and C termini are cytoplasmic, consistent with TRPM channel topology; the ER extends into axons and dendrites but not dendritic tips. Immunofluorescence colocalization with ER markers, fluorescence protease protection (FPP) assay, live imaging of ER-fluorescent marker in bipolar cells eNeuro Medium 30027108
2019 LRIT3 is expressed presynaptically in rod photoreceptors; restoring LRIT3 expression in Lrit3-/- rods (not DBCs) rescues assembly of the postsynaptic glutamate signalplex (including TRPM1) and rod-driven vision, demonstrating that LRIT3 acts as a transsynaptic organizer of the postsynaptic complex containing TRPM1. Cell-type-specific LRIT3 rescue by AAV in Lrit3-/- mice, immunofluorescence, ERG Cell reports High 31189098
2012 A point mutation in the pore domain of TRPM1 (p.A1068T) causes dominant negative inhibition of TRPM1 channel function; heterozygous Trpm1+/tvrm27 mice show reduced b-wave amplitudes and reduced DBC responses to LY341495 or capsaicin, indicating that the number of functional TRPM1 channels at DBC dendritic tips determines DBC response amplitude. Chemical mutagenesis screen, genetic complementation, ERG, whole-cell patch-clamp, immunofluorescence Journal of neurophysiology High 22896717
2017 TRPM1 channel opening is required for rod bipolar cell development and synapse formation with AII amacrine cells: TRPM1-/- mice show contracted rod bipolar terminals, fewer synapses with amacrine cells, and reduced AII amacrine cell dendritic complexity; activated Gαo interacts with TRPM1 and induces contraction of rod bipolar terminals; Channelrhodopsin-2 overexpression partially rescues rod bipolar cell development in TRPM1-/- retina. TRPM1-/- KO mice, immunohistochemistry, morphometric analysis, Co-IP (Gαo-TRPM1), Channelrhodopsin-2 rescue, constitutively closed TRPM1 construct The Journal of neuroscience : the official journal of the Society for Neuroscience High 28899920
2011 TRPM1 current desensitization in ON-bipolar cells depends on the strength of presynaptic stimulus; stimuli activating >20% of maximum TRPM1 current cause desensitization that reduces response to ~40% of peak (time constant ~1 s), with slow recovery (>20 s); TRPM1 desensitization augments the sustained component of downstream ganglion cell EPSCs. Whole-cell patch-clamp of ON-bipolar cells and ganglion cells in retinal slices, dye-filling/morphology The Journal of physiology Medium 22041187
2010 TRPM1 is the endpoint of the mGluR6 signal transduction cascade; reconstitution in CHO cells expressing TRPM1, mGluR6, and Gαo demonstrated that TRPM1 is negatively regulated by the mGluR6/Go cascade. Reconstitution in CHO cells expressing TRPM1, mGluR6, and Gαo; electrophysiology Handbook of experimental pharmacology High 24756714
2022 TRPM1 promotes acral melanoma progression via Ca2+/CaMKIIδ/AKT pathway: TRPM1 elevates cytosolic Ca2+, activates CaMKIIδ, promotes CaMKIIδ/AKT interaction and AKT activation; CaMKII inhibitor (KN93) suppressed TRPM1-driven melanoma cell growth in vitro and in vivo xenograft models. Loss-of-function and gain-of-function (KD/OE), Ca2+ measurement, Western blot for CaMKIIδ/AKT phosphorylation, Co-IP, colony formation, migration/invasion assay, xenograft mouse model Journal of advanced research Medium 36585114
2021 TRPM1 is a client of the HSP90 chaperone; AUY922 (HSP90 inhibitor) reduces TRPM1 expression by disrupting the CDC37-HSP90 chaperone complex, as demonstrated by co-immunoprecipitation of TRPM1 with HSP90. Co-immunoprecipitation, proteomic profiling (iTRAQ), Western blot, loss/gain-of-function assays Journal of biomedical science Medium 34301262
2016 TRPM1 channels are expressed in the lateral amygdala and contribute to capsaicin-induced LTD in the amygdala; using TRPM1-/- mice and pharmacology, capsaicin-induced LTD was absent in TRPM1-/- lateral amygdala; this effect requires group I mGluRs, TRPC5 interaction, and intact GABAergic transmission. Electrophysiology (LTD recordings), TRPM1-/- mice, pharmacological blockers, TRPV1-/- mice Neurobiology of learning and memory Medium 27633915
2013 Anti-TRPM1 antibodies in MAR patient serum cause acute degeneration and apoptosis of retinal ON-bipolar cells in wild-type but not TRPM1-/- mice after intravitreal injection, with reduced ERG amplitudes persisting at 3 months. Intravitreal injection, ERG, immunohistochemistry, TUNEL staining, TRPM1-/- controls PloS one High 24282602
2026 Cryo-EM structure of TRPM1 reveals a canonical tetrameric fold in the intracellular domain but an inverted transmembrane domain with opposite handedness compared to other related channels; the VSLD and pore domain are arranged domain-swapped but with clockwise geometry, forming a large pore-like structure; single-channel recordings show constitutive activity. Cryo-EM, single-particle analysis, single-channel electrophysiology Nature communications High 41857038
2026 Cryo-EM structure of human TRPM1 in conducting state reveals tetrameric assembly with an unexpected clockwise domain-swapped pore module of inverted rotational geometry; this topology is accompanied by a dilated selectivity filter, expanded central cavity, and splayed S6 forming a wide intracellular gate; single-channel recordings confirm constitutive activity. Cryo-EM, single-channel patch-clamp electrophysiology bioRxivpreprint High 41757028
2021 TRPM1 has a functional role in iris sphincter muscle cells: Trpm1-/- mice show severely defective pupillary light reflex (PLR) and iris photomechanical response; light-driven iris constriction independent of brain signaling requires Trpm1 expression and is melanopsin-dependent; capsaicin-driven (pain afferent) iris constriction also requires Trpm1. In vivo PLR measurements in Trpm1-/- mice, isolated eye preparations, pharmacological (capsaicin, melanopsin antagonists) Experimental eye research Medium 34954202
2018 Differential epitope masking by monoclonal antibodies reveals synapse-specific multiprotein complexes of TRPM1 at dendritic tips; antibodies recognizing an N-terminal region (N2d) near the transmembrane domain show reduced labeling at dendritic tips vs. cell bodies, suggesting formation of a synapse-specific complex that masks this epitope. Monoclonal antibody epitope mapping, immunofluorescence, quantitative immunoblotting of synaptosomes Visual neuroscience Low 29370879
2017 MAR autoantibodies recognize an epitope encoded by exons 9 and 10 of TRPM1 that is conserved with TRPM3; MAR sera cross-react with TRPM3 in the retinal pigment epithelium. Immunofluorescence and Western blot on HEK293 cells transfected with EGFP-TRPM1 deletion constructs, retinal section immunostaining Investigative ophthalmology & visual science Medium 28549093

Source papers

Stage 0 corpus · 88 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells. Proceedings of the National Academy of Sciences of the United States of America 260 19861548
2009 TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade. Proceedings of the National Academy of Sciences of the United States of America 246 19966281
2009 TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness. American journal of human genetics 185 19896113
2009 Mutations in TRPM1 are a common cause of complete congenital stationary night blindness. American journal of human genetics 179 19896109
2009 TRPM1 forms ion channels associated with melanin content in melanocytes. Science signaling 159 19436059
2009 Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans. American journal of human genetics 150 19878917
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 TRPM1: the endpoint of the mGluR6 signal transduction cascade in retinal ON-bipolar cells. BioEssays : news and reviews in molecular, cellular and developmental biology 93 20544736
2010 TRPM1 mutations are associated with the complete form of congenital stationary night blindness. Molecular vision 89 20300565
2013 Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse. PloS one 87 24167615
2011 TRPM1 forms complexes with nyctalopin in vivo and accumulates in postsynaptic compartment of ON-bipolar neurons in mGluR6-dependent manner. The Journal of neuroscience : the official journal of the Society for Neuroscience 81 21832182
1998 Chromosomal localization and genomic characterization of the mouse melastatin gene (Mlsn1). Genomics 81 9806836
2011 Identification of autoantibodies against TRPM1 in patients with paraneoplastic retinopathy associated with ON bipolar cell dysfunction. PloS one 75 21611200
2010 TRPM1: a vertebrate TRP channel responsible for retinal ON bipolar function. Cell calcium 75 20846719
2009 Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light. American journal of physiology. Cell physiology 71 19587221
2012 G-protein-mediated inhibition of the Trp channel TRPM1 requires the Gβγ dimer. Proceedings of the National Academy of Sciences of the United States of America 68 22586107
2011 Transient receptor potential melastatin 1 (TRPM1) is an ion-conducting plasma membrane channel inhibited by zinc ions. The Journal of biological chemistry 65 21278253
2011 Autoantibodies in melanoma-associated retinopathy target TRPM1 cation channels of retinal ON bipolar cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 21411639
2004 Human melastatin 1 (TRPM1) is regulated by MITF and produces multiple polypeptide isoforms in melanocytes and melanoma. Melanoma research 55 15577322
2011 mGluR6 deletion renders the TRPM1 channel in retina inactive. Journal of neurophysiology 52 22131384
2015 LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation. The European journal of neuroscience 48 25997951
2010 A 15q13.3 homozygous microdeletion associated with a severe neurodevelopmental disorder suggests putative functions of the TRPM1, CHRNA7, and other homozygously deleted genes. American journal of medical genetics. Part A 47 20425840
2011 Homozygous deletion of chromosome 15q13.3 including CHRNA7 causes severe mental retardation, seizures, muscular hypotonia, and the loss of KLF13 and TRPM1 potentially cause macrocytosis and congenital retinal dysfunction in siblings. European journal of medical genetics 43 21596161
2019 Presynaptic Expression of LRIT3 Transsynaptically Organizes the Postsynaptic Glutamate Signaling Complex Containing TRPM1. Cell reports 42 31189098
2012 Depolarizing bipolar cell dysfunction due to a Trpm1 point mutation. Journal of neurophysiology 41 22896717
2010 Fine-mapping and mutation analysis of TRPM1: a candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses. Briefings in functional genomics 37 20353955
2013 Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes. Pigment cell & melanoma research 36 23452348
2015 Voriconazole, an antifungal triazol that causes visual side effects, is an inhibitor of TRPM1 and TRPM3 channels. Investigative ophthalmology & visual science 35 25650413
2013 Serum TRPM1 autoantibodies from melanoma associated retinopathy patients enter retinal on-bipolar cells and attenuate the electroretinogram in mice. PloS one 35 23936334
2020 Role of the p53‑TRPM1/miR‑211‑MMP9 axis in UVB‑induced human melanocyte migration and its potential in repigmentation. International journal of molecular medicine 34 31985026
2016 The TRPM1 channel in ON-bipolar cells is gated by both the α and the βγ subunits of the G-protein Go. Scientific reports 33 26883481
2010 The correlation of TRPM1 (Melastatin) mRNA expression with microphthalmia-associated transcription factor (MITF) and other melanogenesis-related proteins in normal and pathological skin, hair follicles and melanocytic nevi. Journal of cutaneous pathology 33 20482673
2015 Properties and functions of TRPM1 channels in the dendritic tips of retinal ON-bipolar cells. European journal of cell biology 29 26111660
2011 Relief of Mg²⁺-dependent inhibition of TRPM1 by PKCα at the rod bipolar cell synapse. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 21940450
2019 Synaptotagmin-4 promotes dendrite extension and melanogenesis in alpaca melanocytes by regulating Ca2+ influx via TRPM1 channels. Cell biochemistry and function 26 31743468
2011 Ultrastructural localization and expression of TRPM1 in the human retina. Investigative ophthalmology & visual science 26 21896854
2016 A novel synthetic Piper amide derivative NED-180 inhibits hyperpigmentation by activating the PI3K and ERK pathways and by regulating Ca2+ influx via TRPM1 channels. Pigment cell & melanoma research 25 26459162
2017 Autoantibodies in Melanoma-Associated Retinopathy Recognize an Epitope Conserved Between TRPM1 and TRPM3. Investigative ophthalmology & visual science 24 28549093
2009 In with the TRP channels: intracellular functions for TRPM1 and TRPM2. Science signaling 24 19887679
2022 TRPM1 promotes tumor progression in acral melanoma by activating the Ca2+/CaMKIIδ/AKT pathway. Journal of advanced research 22 36585114
2018 A Large Endoplasmic Reticulum-Resident Pool of TRPM1 in Retinal ON-Bipolar Cells. eNeuro 22 30027108
2017 Joint Analysis of Nuclear and Mitochondrial Variants in Age-Related Macular Degeneration Identifies Novel Loci TRPM1 and ABHD2/RLBP1. Investigative ophthalmology & visual science 22 28813576
2014 Oligomeric state of purified transient receptor potential melastatin-1 (TRPM1), a protein essential for dim light vision. The Journal of biological chemistry 22 25112866
2017 The TRPM1 Channel Is Required for Development of the Rod ON Bipolar Cell-AII Amacrine Cell Pathway in the Retinal Circuit. The Journal of neuroscience : the official journal of the Society for Neuroscience 21 28899920
2014 TRPM1. Handbook of experimental pharmacology 21 24756714
2009 TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular melanomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 21 19396153
2020 Novel three-way complex rearrangement of TRPM1-PUM1-LCK in a case of agminated Spitz nevi arising in a giant congenital hyperpigmented macule. Pigment cell & melanoma research 19 32386465
2019 TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations. Scientific reports 19 31427709
2015 Alterations in Kainate Receptor and TRPM1 Localization in Bipolar Cells after Retinal Photoreceptor Degeneration. Frontiers in cellular neuroscience 19 26733812
2014 Further delineation of eye manifestations in homozygous 15q13.3 microdeletions including TRPM1: a differential diagnosis of ceroid lipofuscinosis. American journal of medical genetics. Part A 19 24668847
2011 TRPM1: new trends for an old TRP. Advances in experimental medicine and biology 19 21290293
2013 Diagnosis of occult melanoma using transient receptor potential melastatin 1 (TRPM1) autoantibody testing: a novel approach. Ophthalmology 17 24053997
2013 Degeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy. PloS one 17 24282602
2021 AUY922 induces retinal toxicity through attenuating TRPM1. Journal of biomedical science 16 34301262
2020 Identification and characterization of novel TRPM1 autoantibodies from serum of patients with melanoma-associated retinopathy. PloS one 16 32324760
2019 CLINICAL COURSE OF PARANEOPLASTIC RETINOPATHY WITH ANTI-TRPM1 AUTOANTIBODY IN JAPANESE COHORT. Retina (Philadelphia, Pa.) 16 30260920
2019 TRPM1 Autoantibodies in Melanoma Patients Without Self-Reported Visual Symptoms. Investigative ophthalmology & visual science 14 31117125
2018 Different Activity Patterns in Retinal Ganglion Cells of TRPM1 and mGluR6 Knockout Mice. BioMed research international 14 29854741
2010 Plasticity of TRPM1 expression and localization in the wild type and degenerating mouse retina. Vision research 14 20801142
2014 Choroidal atrophy in a patient with paraneoplastic retinopathy and anti-TRPM1 antibody. Clinical ophthalmology (Auckland, N.Z.) 11 24523577
2022 Clinical and genetic findings in TRPM1-related congenital stationary night blindness. Acta ophthalmologica 10 35633130
2019 Long-term follow-up of retinal function and structure in TRPM1-associated complete congenital stationary night blindness. Molecular vision 10 31908403
2018 Differential epitope masking reveals synapse-specific complexes of TRPM1. Visual neuroscience 10 29370879
2012 Mutation screening of TRPM1, GRM6, NYX and CACNA1F genes in patients with congenital stationary night blindness. International journal of molecular medicine 10 22735794
2021 Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior. Molecular brain 9 33785025
2020 Novel biallelic TRPM1 variants in an elderly patient with complete congenital stationary night blindness. Documenta ophthalmologica. Advances in ophthalmology 9 33068213
2020 A case of melanoma-associated retinopathy with autoantibodies against TRPM1. Documenta ophthalmologica. Advances in ophthalmology 8 32472235
2016 Heterogeneity of Metastatic Melanoma:  Correlation of MITF With Its Transcriptional Targets MLSN1, PEDF, HMB-45, and MART-1. American journal of clinical pathology 8 27515936
2016 A novel form of capsaicin-modified amygdala LTD mediated by TRPM1. Neurobiology of learning and memory 8 27633915
2016 Novel TRPM1 mutations in two Chinese families with early-onset high myopia, with or without complete congenital stationary night blindness. International journal of ophthalmology 8 27803854
2015 Characterization of the part of N-terminal PIP2 binding site of the TRPM1 channel. Biophysical chemistry 8 26544986
2011 Characterization of Trpm1 desensitization in ON bipolar cells and its role in downstream signalling. The Journal of physiology 8 22041187
2021 Clinical Findings of Melanoma-Associated Retinopathy with anti-TRPM1 Antibody. Case reports in ophthalmological medicine 7 34540301
2016 The characterization of a novel S100A1 binding site in the N-terminus of TRPM1. The international journal of biochemistry & cell biology 7 27435061
2022 Melanoma-associated retinopathy with anti-TRPM1 autoantibodies showing concomitant Off-bipolar cell dysfunction. Documenta ophthalmologica. Advances in ophthalmology 5 36173494
2021 Broad locations of antigenic regions for anti-TRPM1 autoantibodies in paraneoplastic retinopathy with retinal ON bipolar cell dysfunction. Experimental eye research 5 34562437
2024 Anti-TRPM1 autoantibody-positive unilateral melanoma associated retinopathy (MAR) triggered by immunotherapy recapitulates functional and structural details of TRPM1-associated congenital stationary night blindness. American journal of ophthalmology case reports 4 39109318
2022 Glucocorticoid Exposure of Preimplantation Embryos Increases Offspring Anxiety-Like Behavior by Upregulating miR-211-5p via Trpm1 Demethylation. Frontiers in cell and developmental biology 4 35433692
2019 A founder deletion in the TRPM1 gene associated with congenital stationary night blindness and myopia is highly prevalent in Ashkenazi Jews. Human genome variation 4 31645983
2022 Unilateral cataract and congenital stationary night blindness in a child with novel variants in TRPM1. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus 2 35872165
2021 Congenital stationary night blindness in a patient with mild learning disability due to a compound heterozygous microdeletion of 15q13 and a missense mutation in TRPM1. Ophthalmic genetics 2 33691579
2021 Trpm1: Novel function at the intersection of light and pain response in the iris. Experimental eye research 2 34954202
2011 Genetic variants in transient receptor potential cation channel, subfamily M 1 (TRPM1) and their risk of albuminuria-related traits in Mexican Americans. Clinica chimica acta; international journal of clinical chemistry 2 21439949
2025 New insights into sex determination in amphibians: Unraveling the regulatory roles of Trpm1 and Dmrt1 in the Chinese giant salamander (Andrias davidianus). International journal of biological macromolecules 1 40882735
2020 Association Analysis Between Common Variants of the TRPM1 Gene and Three Mental Disorders in the Han Chinese Population. Genetic testing and molecular biomarkers 1 33001715
2026 Unique pore architecture underlies constitutive gating of human retinal TRPM1. bioRxiv : the preprint server for biology 0 41757028
2026 Cryo-EM structure of TRPM1 reveals a non-canonical architecture with an inverted transmembrane domain. Nature communications 0 41857038
2026 Upregulated TRPM1 is associated with apoptosis in Rs1 knockout mice and in ARPE19 cells through increased intracellular calcium. Scientific reports 0 41942595