Affinage

TRPM1

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

Length
1603 aa
Mass
182.2 kDa
Annotated
2026-06-10
89 papers in source corpus 33 papers cited in narrative 34 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

TRPM1 is a constitutively active, nonselective cation channel that serves as the effector channel of the depolarizing light response in retinal ON-bipolar cells, where its genetic deletion abolishes the ERG b-wave and the photoresponse (PMID:19861548, PMID:19966281). Localized to the dendritic tips of ON-bipolar cells co-localizing with mGluR6, TRPM1 is gated by the mGluR6–Go cascade: it is closed when Go is activated, with both Gβγ dimer and the constitutively active form of Gαo binding and cooperating to close the channel—Gβγ interacting with the N-terminus and Gαo with both N- and C-termini—while sequestration of Gβγ opens it (PMID:19966281, PMID:22586107, PMID:26883481). Channel activity is further tuned by relief of voltage-independent intracellular Mg2+ inhibition through PKCα activation, which raises synaptic transmission gain, and by use-dependent desensitization that shapes downstream ganglion cell responses (PMID:21940450, PMID:22041187). Targeting of TRPM1 to the postsynaptic dendritic-tip signalplex requires a transsynaptic scaffold: TRPM1 forms an in vivo complex with nyctalopin, its localization is mGluR6-dependent, and presynaptic LRIT3—via its IG domain—organizes signalplex assembly and TRPM1 retention at the synapse (PMID:21832182, PMID:22131384, PMID:25997951, PMID:31189098). Beyond gating, channel opening drives the developmental wiring of the rod ON-bipolar–AII amacrine pathway, and TRPM1 also functions in the iris sphincter muscle to mediate the pupillary light reflex (PMID:28899920, PMID:34954202). Structurally, TRPM1 is a tetrameric channel with a non-canonical, inverted domain-swapped transmembrane arrangement and a wide conductive pore (PMID:41857038). In melanocytes TRPM1 conducts Ca2+, supports Ca2+ homeostasis and melanogenesis under MITF transcriptional control, and is positively coupled to mGluR6—a tissue-specific reversal of its retinal polarity explained by the relative absence of Gαo (PMID:19436059, PMID:19587221, PMID:15577322, PMID:23452348). Clinically, TRPM1 is the autoantigen in melanoma-associated retinopathy, where patient autoantibodies are taken up by ON-bipolar cells in a TRPM1-dependent manner, attenuate the b-wave, and drive ON-bipolar cell degeneration (PMID:21411639, PMID:23936334, PMID:24282602).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2009 High

    Established TRPM1 as the long-sought effector channel of the retinal ON-bipolar cell light response, answering what carries the depolarizing current downstream of mGluR6.

    Evidence TRPM1 knockout mouse ERG and patch-clamp of ON-bipolar cells, immunolocalization with mGluR6, and heterologous reconstitution with Go manipulation

    PMID:19861548 PMID:19966281

    Open questions at the time
    • Did not define which Go subunit (Gα vs Gβγ) closes the channel
    • Mechanism of constitutive activity not resolved
  2. 2009 Medium

    Showed TRPM1 conducts an endogenous cation current in melanocytes and supports Ca2+-dependent melanogenesis, extending its function beyond retina to pigment biology.

    Evidence Endogenous current recording, microRNA and shRNA knockdown, Ca2+ and tyrosinase/melanin assays, p53 repression in primary human melanocytes and melanoma cells

    PMID:19436059 PMID:19587221

    Open questions at the time
    • Predominantly intracellular vesicular localization in melanoma cells leaves plasma-membrane gating unclear
    • Single-lab functional readouts
  3. 2004 Medium

    Identified MITF-driven, E-box/M-box-dependent melanocyte-specific transcription of TRPM1 and multiple splice/cleavage isoforms, defining how the gene is regulated in pigment cells.

    Evidence Promoter deletion analysis, MITF activation assay, Western blot in melanocytes/melanoma cells

    PMID:15577322

    Open questions at the time
    • Functional roles of distinct isoforms not assigned
    • Retinal transcriptional control not addressed
  4. 2011 High

    Demonstrated that TRPM1 is a plasma-membrane channel that can heteromultimerize with TRPM3 and is inhibited by extracellular zinc through a defined pore stretch, characterizing intrinsic channel properties.

    Evidence Heterologous expression patch-clamp, pore mutagenesis, heteromultimer co-expression, zinc inhibition assays

    PMID:21278253

    Open questions at the time
    • Physiological relevance of TRPM1/TRPM3 heteromers in retina not established
    • Did not address native gating by G-proteins
  5. 2011 High

    Defined the transsynaptic scaffolding required to deliver TRPM1 to the dendritic-tip signalplex, answering how the channel is positioned at the synapse.

    Evidence Proteomic pulldown of TRPM1–nyctalopin complex from retina and immunolocalization in mGluR6-knockout retina; capsaicin testing in mGluR6-null bipolar cells

    PMID:21832182 PMID:22131384

    Open questions at the time
    • Did not identify the factor conferring constitutive activity
    • Direct binding interfaces not mapped
  6. 2012 High

    Resolved the G-protein gating mechanism, showing Gβγ (and later cooperatively Gαo) closes TRPM1 and defining the N-/C-terminal interaction sites.

    Evidence Intracellular dialysis of Gβγ/Gαo across multiple cell types, GPCR pharmacology, BRET and Co-IP

    PMID:22586107 PMID:26883481

    Open questions at the time
    • Structural basis of G-protein-induced closure not visualized
    • Stoichiometry of G-protein:channel binding unresolved
  7. 2011 High

    Showed PKCα and use-dependent desensitization tune TRPM1 gain and kinetics, explaining synaptic signal shaping at the rod-bipolar synapse.

    Evidence Patch-clamp with DAG analog, PKCα knockout, Mg2+ manipulation, and ganglion cell EPSC recordings

    PMID:21940450 PMID:22041187

    Open questions at the time
    • PKCα phosphorylation site on TRPM1 not identified
    • Molecular basis of desensitization unknown
  8. 2011 High

    Identified TRPM1 as the autoantigen in melanoma-associated retinopathy, linking the channel to a paraneoplastic disease.

    Evidence MAR serum immunofluorescence on TRPM1-transfected and Grm6-GFP cells, Western blot, Trpm1-/- negative control

    PMID:21411639

    Open questions at the time
    • Precise intracellular epitope not finely mapped here
    • Pathogenic mechanism not yet demonstrated in vivo
  9. 2012 High

    Provided a disease-relevant pore mutation (A1068T) acting as a dominant negative, validating the pore domain's role in channel function and bipolar cell dysfunction.

    Evidence ENU mutagenesis, complementation testing with Trpm1-/-, sequencing, patch-clamp and ERG

    PMID:22896717

    Open questions at the time
    • Structural consequence of A1068T not determined
    • Human genotype correlation not addressed here
  10. 2013 High

    Demonstrated that MAR autoantibodies are internalized via TRPM1 and cause TRPM1-dependent ON-bipolar cell dysfunction and degeneration, establishing disease causation.

    Evidence Intravitreal IgG/serum injection in wild-type vs Trpm1-/- mice, ERG, TUNEL, INL thickness, live-neuron uptake assays

    PMID:23936334 PMID:24282602

    Open questions at the time
    • Mechanism by which internalized antibody impairs/destroys cells unresolved
    • Whether antibody blocks channel directly not determined
  11. 2013 Medium

    Explained the tissue-specific reversal of TRPM1–mGluR6 coupling, showing positive coupling in melanocytes that converts to negative coupling upon Gαo expression.

    Evidence shRNA knockdown of TRPM1/mGluR6, Ca2+ imaging, patch-clamp, forced Gαo expression, pertussis toxin in melanocytes

    PMID:23452348

    Open questions at the time
    • Single-lab finding
    • Endogenous melanocyte G-protein milieu not fully characterized
  12. 2014 High

    Provided the first biophysical/structural insight into TRPM1 assembly, showing a recombinant dimer plus a larger native complex, indicating additional native subunits.

    Evidence Recombinant purification, blue native gels, SEC, cross-linking, cryo-EM single-particle analysis, native retina complexes

    PMID:25112866

    Open questions at the time
    • Identity of additional native subunits not determined
    • Dimer vs tetramer discrepancy with later structures unresolved at the time
  13. 2015 Medium

    Established LRIT3 as essential for dendritic-tip localization of TRPM1, deepening the model of signalplex assembly.

    Evidence Immunofluorescence of Lrit3 knockout retina with TRPM1 antibody

    PMID:25997951

    Open questions at the time
    • Direct LRIT3–TRPM1 binding not shown in this study
    • Mechanism of localization downstream of LRIT3 unclear
  14. 2019 High

    Defined LRIT3 as a presynaptic transsynaptic organizer whose rod-specific restoration rescues the postsynaptic signalplex and vision, clarifying directional assembly.

    Evidence rAAV rod-specific LRIT3 expression in Lrit3-/-, signalplex immunofluorescence, ERG

    PMID:31189098

    Open questions at the time
    • Molecular interactions bridging presynaptic LRIT3 to postsynaptic TRPM1 not detailed here
  15. 2017 High

    Revealed a developmental role for TRPM1 channel opening in wiring the rod bipolar–AII amacrine pathway, beyond acute signal transduction.

    Evidence Comparative morphology across Trpm1, mGluR6, VGluT1 knockouts, Channelrhodopsin-2 rescue, constitutively closed TRPM1, Co-IP of Gαo

    PMID:28899920

    Open questions at the time
    • Downstream signaling linking channel activity to synaptic morphogenesis unknown
  16. 2018 Medium

    Showed most TRPM1 resides in the ER rather than the plasma membrane and that both termini are cytoplasmic, refining channel topology and trafficking.

    Evidence Confocal co-localization with ER/Golgi markers, fluorescence protease protection assay, retina immunostaining

    PMID:30027108

    Open questions at the time
    • Functional role of the ER-resident pool not defined
    • Trafficking signals controlling surface delivery unknown
  17. 2016 Low

    Identified candidate N-terminal regulatory ligand-binding sites for PIP2 and Ca2+-dependent S100A1, suggesting additional modulatory inputs to the channel.

    Evidence Fluorescence spectroscopy, mutagenesis and molecular modeling on recombinant N-terminal TRPM1 fragments

    PMID:26544986 PMID:27435061

    Open questions at the time
    • In vitro fragment binding only, no functional channel validation
    • Physiological relevance in intact channel unestablished
  18. 2021 Medium

    Defined TRPM1 as an HSP90/CDC37 client whose chaperone-dependent stability links it to apoptosis and ROS regulation in cells.

    Evidence Co-IP of TRPM1 with HSP90/CDC37, HSP90 inhibitor, loss/gain-of-function, iTRAQ, TUNEL, ROS assays

    PMID:34301262

    Open questions at the time
    • Single-lab finding
    • Relevance to retinal TRPM1 folding not tested
  19. 2021 Medium

    Extended TRPM1 function to the iris sphincter muscle and pupillary light reflex, demonstrating roles outside ON-bipolar cells.

    Evidence Trpm1 knockout PLR measurements, isolated eye light response, capsaicin pharmacology

    PMID:34954202

    Open questions at the time
    • Molecular pathway in iris muscle not defined
    • Single-lab phenotype
  20. 2016 Medium

    Demonstrated TRPM1 expression and function in the lateral amygdala modulating LTD, identifying a brain role distinct from TRPV1.

    Evidence LTD electrophysiology in Trpm1-/- mice with TRPV1 and group I mGluR pharmacology

    PMID:27633915

    Open questions at the time
    • Mechanism linking TRPM1 to TRPC5 and group I mGluRs unresolved
    • Single-lab finding
  21. 2022 Medium

    Linked melanocyte TRPM1 Ca2+ signaling to acral melanoma progression through a CaMKIIδ–AKT axis, defining an oncogenic mechanism.

    Evidence Loss/gain-of-function in melanoma cells, Western blot, migration/invasion/colony assays, CaMKII inhibitor, xenografts

    PMID:36585114

    Open questions at the time
    • Direct CaMKIIδ activation by TRPM1-mediated Ca2+ not biochemically isolated
    • Single-lab study
  22. 2026 High

    Resolved the TRPM1 structure as a tetramer with a non-canonical inverted, domain-swapped transmembrane fold and a wide conductive pore, explaining its constitutive activity.

    Evidence Cryo-EM structural determination of purified TRPM1 and human TRPM1 in conducting state with single-channel recordings

    PMID:41757028 PMID:41857038

    Open questions at the time
    • Structural basis of G-protein-induced closure not captured
    • Conformational changes during gating not visualized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the mGluR6–Go–Gβγ/Gαo gating signal is structurally transmitted to open and close the inverted TRPM1 pore, and the full composition of the native dendritic-tip signalplex, remain unresolved.
  • No closed-state structure with bound G-proteins
  • Additional native subunits beyond nyctalopin/LRIT3 not identified
  • Mechanism converting channel activity to developmental wiring unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-9709957 Sensory Perception 2
Partners
CDC37GNAO1GRM6HSP90LRIT3NYXPRKCATRPM3
Complex memberships
HSP90–CDC37 chaperone complexTRPM1–nyctalopin–mGluR6 dendritic-tip signalplex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells; genetic deletion of TRPM1 abolishes chemically simulated light responses from rod bipolar cells, and TRPM1 protein localizes to the dendrites of ON-bipolar cells in mouse and macaque retina. TRPM1 knockout mouse (ERG showing loss of b-wave), whole-cell patch-clamp recording from ON-bipolar cells in retinal slices, immunofluorescent confocal microscopy, in situ hybridization Proceedings of the National Academy of Sciences of the United States of America High 19861548
2009 The long form of TRPM1 (TRPM1-L) functions as a constitutively active nonselective cation channel in ON-bipolar cells, localizes specifically to the dendritic tips of ON-bipolar cells co-localizing with mGluR6, and its activity is negatively regulated by Go in the mGluR6 cascade. TRPM1 null mice completely lose the photoresponse of ON-bipolar cells. TRPM1 null mouse ERG and patch-clamp recordings, immunolocalization with mGluR6 co-staining, heterologous expression in TRPM1-L-expressing cells with Go manipulation Proceedings of the National Academy of Sciences of the United States of America High 19966281
2009 TRPM1 forms an endogenous ion channel current in primary human neonatal epidermal melanocytes and mouse melanoma cells; knockdown by microRNA directed against TRPM1 abolished this current. In melanoma cells, TRPM1 is prevalent in highly dynamic intracellular vesicular structures rather than at the plasma membrane. Endogenous current recording in primary melanocytes, microRNA-mediated knockdown, subcellular localization by live imaging Science signaling Medium 19436059
2009 TRPM1 knockdown by lentiviral shRNA in human melanocytes reduces intracellular Ca2+ levels, decreases Ca2+ uptake, reduces tyrosinase activity and intracellular melanin, establishing a role for TRPM1 in Ca2+ homeostasis and melanogenesis. p53 overexpression or UVB-induced p53 represses TRPM1 expression with concomitant decrease in Ca2+ mobilization. Lentiviral shRNA knockdown, intracellular Ca2+ measurements, tyrosinase activity assay, melanin quantification, p53 transfection and UVB treatment American journal of physiology. Cell physiology Medium 19587221
2004 TRPM1 (MLSN1) promoter contains four E-boxes including an M-box; a 654 bp upstream sequence containing two distal E-boxes (E3 and E4) is sufficient for melanocyte-specific transcription and is activated by the transcription factor MITF. Multiple TRPM1 polypeptide isoforms are generated by alternative splicing and proteolytic cleavage in melanocytes and melanoma cells. Promoter deletion analysis, MITF activation assay, Western blot with anti-MLSN1 antibody Melanoma research Medium 15577322
2011 TRPM1 forms a complex with nyctalopin in vivo in the mouse retina (identified by proteomic pulldown from retinal lysates); nyctalopin also interacts with mGluR6. Disruption of mGluR6 prevents targeting of TRPM1 to the postsynaptic compartment of ON-bipolar neurons, indicating mGluR6-dependent localization of TRPM1. Proteomic search (Co-IP/pulldown from mouse retina), immunolocalization in mGluR6 knockout retina The Journal of neuroscience : the official journal of the Society for Neuroscience High 21832182
2012 Gβγ dimer, but not Gαo, closes TRPM1 channels in rod bipolar cells, human epidermal melanocytes endogenously expressing TRPM1, and HEK293 cells transfected with TRPM1. Dialysis of Gβγ into cells closed TRPM1 channels; activation of an endogenous GPCR pathway releasing Gβγ without activating Go also closed TRPM1. Whole-cell patch-clamp with intracellular dialysis of Gβγ or Gαo in multiple cell types; pharmacological GPCR activation in HEK293 cells Proceedings of the National Academy of Sciences of the United States of America High 22586107
2011 TRPM1 is an ion-conducting plasma membrane channel. Heterologous TRPM1 expression induces ionic conductances; TRPM1 and TRPM3 form functional heteromultimeric channels. Channels containing the pore of TRPM1 are inhibited by extracellular zinc ions at physiological concentrations, mediated by a seven-amino-acid stretch specific to the pore region of TRPM1. Heterologous expression and patch-clamp electrophysiology, mutagenesis of pore region, heteromultimer co-expression, zinc inhibition assays The Journal of biological chemistry High 21278253
2011 In mGluR6-null rod bipolar cells, the TRPM1 channel is inactive despite partial plasma membrane localization; TRPM1 immunostaining at the dendritic tips is greatly reduced in mGluR6-null retina but remains in soma and primary dendrites. Capsaicin failed to activate TRPM1 in null cells, suggesting the channel requires a complex or unknown factor to be constitutively active. Whole-cell patch-clamp in mGluR6 knockout retinal slices, capsaicin local application, immunostaining for TRPM1 and G-protein subunits Journal of neurophysiology High 22131384
2011 Autoantibodies in melanoma-associated retinopathy (MAR) target TRPM1 cation channels of retinal ON-bipolar cells. MAR sera label TRPM1-transfected HEK cells, produce expected 180 kDa band on Western blot, colocalize with GFP in Grm6-GFP ON-bipolar cells, and do not stain Trpm1-/- retina. The targeted epitope is intracellular, and sera can be internalized by retinal cells. Immunofluorescence on TRPM1-transfected cells and retinal sections, Western blot, Trpm1-/- negative control, co-localization with Gαo and Grm6-GFP The Journal of neuroscience : the official journal of the Society for Neuroscience High 21411639
2013 Intravitreal injection of MAR IgG (TRPM1-positive) into wild-type mouse eyes attenuated the ERG b-wave and IgG appeared in retinal ON-bipolar cells at experiment's end; this effect was absent in Trpm1-/- mice. Live incubation of retinal neurons with TRPM1-positive MAR serum resulted in selective IgG accumulation in ON-bipolar cells, dependent on TRPM1 expression, indicating autoantibody uptake via TRPM1 reduces ON-bipolar cell function. Intravitreal IgG injection with ERG recording, immunofluorescence in wild-type vs. Trpm1-/- retina, live-neuron incubation assay PloS one High 23936334
2011 PKCα activation by DAG (via OAG analog) potentiates TRPM1 current in rod bipolar cells but not ON-cone bipolar cells. TRPM1 current is susceptible to voltage-independent inhibition by intracellular Mg2+, and PKCα activation relieves this Mg2+ inhibition, increasing transmission gain at the rod-rod bipolar cell synapse. Whole-cell patch-clamp of rod and cone bipolar cells with pharmacological DAG analog application; PKCα knockout mice; PKCα inhibitor; manipulation of intracellular Mg2+ The Journal of neuroscience : the official journal of the Society for Neuroscience High 21940450
2016 Both Gαo (constitutively active form) and Gβγ bind and cooperate to close TRPM1 channels in rod bipolar cells. Phosducin or inactive Gαo (both sequester Gβγ) opened the channel. Bioluminescent energy transfer (BRET) assays revealed Gαo interacts with both N- and C-termini of TRPM1, while Gβγ interacts only with the N-terminus. Co-immunoprecipitation confirmed TRPM1 interaction with Gβ3 and active/inactive forms of Gαo. Intracellular dialysis in rod bipolar cells, BRET assay, Co-immunoprecipitation Scientific reports High 26883481
2014 Purified recombinant TRPM1 exists predominantly as a dimer (not tetramer) as shown by blue native gels, size exclusion chromatography, cross-linking, and cryo-EM single-particle analysis with approximate 2-fold symmetry. In mouse retina, TRPM1 is present in two distinct complexes: one matching the recombinant dimer size and one much larger, suggesting additional partner subunits participate in the native transduction channel. Insect cell recombinant expression, affinity purification, blue native gels, size exclusion chromatography, chemical cross-linking, cryoelectron microscopy with single-particle analysis The Journal of biological chemistry High 25112866
2015 LRIT3 is essential for the localization of TRPM1 to the dendritic tips of depolarizing bipolar cells; in Lrit3nob6/nob6 mice, TRPM1 staining at the dendritic tips was severely decreased across all ON-bipolar cell types. Immunofluorescence confocal microscopy of Lrit3 knockout mouse retina sections with TRPM1 antibody The European journal of neuroscience Medium 25997951
2019 LRIT3 is expressed presynaptically in rod photoreceptors and acts as a transsynaptic organizer; restoration of LRIT3 expression in Lrit3-/- rods (by rAAV) restores postsynaptic glutamate signalplex including TRPM1 and rescues rod-driven vision. rAAV-mediated rod-specific LRIT3 expression in Lrit3-/- retina, immunofluorescence of TRPM1 and other signalplex components, ERG Cell reports High 31189098
2012 A point mutation in the pore domain of TRPM1 (A1068T, exon 23) causes depolarizing bipolar cell dysfunction. This mutant TRPM1 protein is retained at dendritic tips but acts as a dominant negative, reducing channel function in heterozygous animals by ~32%. Chemical mutagenesis screen (ENU), complementation testing with Trpm1-/- mice, sequencing, whole-cell patch-clamp, ERG Journal of neurophysiology High 22896717
2013 In human melanocytes, mGluR6 signaling positively (not negatively) enhances TRPM1 Ca2+ channel activity and increases melanin content; shRNA knockdown of TRPM1 or mGluR6 abolished L-AP4-induced Ca2+ influx and TRPM1 currents. Forced expression of Gαo in melanocytes restored negative coupling of TRPM1 to mGluR6, explaining the tissue-specific difference from retina. shRNA knockdown of TRPM1 and mGluR6, Ca2+ imaging, patch-clamp, Gαo forced expression, pertussis toxin treatment Pigment cell & melanoma research Medium 23452348
2011 Ultrastructural immunoelectron microscopy in human retina localizes TRPM1 immunoreactivity specifically to the tips of ON-bipolar cell dendrites that invaginate cone pedicles and rod spherules. TRPM1 immunoreactivity was also occasionally found on rod spherule ribbons, suggesting a possible dual function. Immunohistochemistry at light and electron microscope level, in situ hybridization, laser dissection microscopy PCR Investigative ophthalmology & visual science Medium 21896854
2015 Voriconazole, an antifungal agent causing visual side effects, inhibits TRPM1 channels in retinal ON-bipolar cells; it almost completely blocked capsaicin-activated TRPM1 currents and inhibited ON-bipolar cell responses evoked by mGluR6 antagonist CPPG. In contrast, voriconazole only slightly inhibited mGluR6-mediated GIRK currents, identifying TRPM1 (not mGluR6) as the primary retinal target. Mouse ERG before/after intraperitoneal voriconazole; patch-clamp of ON-bipolar cells; patch-clamp of CHO/HEK cells expressing TRPM3 or mGluR6+GIRK Investigative ophthalmology & visual science High 25650413
2011 TRPM1 current in ON-bipolar cells undergoes use-dependent desensitization; desensitization onset is linear above a ~20% activation threshold, reducing responses to ~40% of peak with a time constant of ~1 s, with slow recovery (>20 s). This desensitization shapes the kinetics of downstream ganglion cell EPSCs by curtailing their sustained component. Whole-cell patch-clamp of ON-bipolar cells and ganglion cells in mouse retinal slices The Journal of physiology Medium 22041187
2017 TRPM1 channel opening is required for the development of the rod ON bipolar cell–AII amacrine cell pathway; deletion of TRPM1 causes abnormal contraction of rod bipolar terminals and decreased synaptic connections with amacrine cells, as well as reduced AII amacrine cell dendritic complexity. Activated Gαo interacts with TRPM1 and induces contraction of rod bipolar terminals. Overexpression of Channelrhodopsin-2 partially rescued rod bipolar development in TRPM1-/- retina. TRPM1 knockout, mGluR6 knockout, VGluT1 knockout mouse morphological comparisons; Channelrhodopsin-2 overexpression rescue; constitutively closed TRPM1 form; Co-IP of Gαo with TRPM1 The Journal of neuroscience : the official journal of the Society for Neuroscience High 28899920
2018 The majority of TRPM1 in ON-bipolar cells resides in the endoplasmic reticulum (ER), not at the plasma membrane; TRPM1 colocalizes with ER markers in both heterologous cells and native mouse bipolar cell bodies, but is excluded from the Golgi. Fluorescence protease protection assays showed that both N and C termini of TRPM1 are cytoplasmic. Confocal co-localization with ER/Golgi markers, fluorescence protease protection (FPP) assay with TRPM1-GFP fusions in heterologous cells, immunostaining of mouse retina eNeuro Medium 30027108
2015 The N-terminal region of TRPM1 (residues A451-N566) contains a PIP2-binding site; the residue K464 is involved in PIP2 interactions, characterized by biophysical methods and molecular modeling. Biophysical methods (fluorescence spectroscopy) and molecular modeling on recombinant N-terminal TRPM1 fragment Biophysical chemistry Low 26544986
2016 The N-terminal region L242-E344 of TRPM1 is an S100A1 binding domain; complex formation is calcium-dependent and is mediated by positively charged (K271, R273, R274) and hydrophobic (L263, V270, L276) residues at the N-terminus. Fluorescence spectroscopy, bioinformatics, mutagenesis of N-terminal TRPM1 fragment The international journal of biochemistry & cell biology Low 27435061
2021 TRPM1 is a bona fide HSP90 client protein; AUY922 (HSP90 inhibitor) reduces TRPM1 expression by disrupting the CDC37-HSP90 chaperone complex as demonstrated by co-immunoprecipitation. Loss of TRPM1 mediates AUY922-induced cell apoptosis, ROS production and growth inhibition. Co-immunoprecipitation of TRPM1 with HSP90/CDC37, loss-of-function and gain-of-function in cells, iTRAQ proteomics, TUNEL, ROS assay Journal of biomedical science Medium 34301262
2022 TRPM1 promotes acral melanoma tumor progression by elevating cytosolic Ca2+ levels, activating CaMKIIδ, promoting CaMKIIδ/AKT interaction and AKT activation. CaMKII inhibitor KN93 suppressed TRPM1-dependent colony formation, cell migration, invasion and xenograft tumor growth. Loss-of-function and gain-of-function in melanoma cells, Western blotting, colony formation, migration/invasion assays, xenograft mouse models, Ca2+ measurement Journal of advanced research Medium 36585114
2021 TRPM1 has a functional role in the iris sphincter muscle; Trpm1-/- mice show severely reduced pupillary light reflex at both scotopic and photopic intensities, attributable to loss of TRPM1 in both the retina and iris sphincter muscle. Light-driven iris constriction independent of brain signaling also requires Trpm1. Capsaicin-driven (sensory) iris constriction also requires Trpm1 expression, implicating TRPM1 in pain-afferent-driven iris responses. Trpm1 knockout mice, in vivo PLR measurements, isolated eye light response assays, capsaicin pharmacology Experimental eye research Medium 34954202
2016 Capsaicin activates TRPM1 channels in the lateral amygdala to modify LTD, via a mechanism independent of TRPV1 and involving group I mGluRs and TRPC5. This effect was absent in TRPM1-/- mice, demonstrating TRPM1 expression and function in the brain. Electrophysiology (LTD measurement) in TRPM1-/- mice, pharmacological profiling with TRPV1 antagonists and group I mGluR blockers Neurobiology of learning and memory Medium 27633915
2018 Differential epitope masking by monoclonal antibodies reveals that a specific N-terminal epitope (N2d) near the transmembrane domain of TRPM1 is masked at the dendritic tips but accessible in cell bodies, suggesting formation of a synapse-specific multiprotein complex at the dendritic tip pool of TRPM1. Monoclonal antibody epitope mapping, differential immunostaining of retinal soma vs. dendritic tips, quantitative immunoblotting of synaptosome fractions Visual neuroscience Low 29370879
2013 Anti-TRPM1 serum from a paraneoplastic retinopathy patient, injected intravitreally into wild-type mice, caused acute death of retinal ON-bipolar cells within 5 hours (TUNEL-positive) and chronic inner nuclear layer thinning at 3 months; no bipolar cell death was observed in TRPM1 knockout mice, confirming TRPM1-dependent antibody-mediated ON-bipolar cell degeneration. Intravitreal serum injection in wild-type and TRPM1 KO mice, ERG, TUNEL staining, immunohistochemistry, INL thickness measurement PloS one High 24282602
2026 Cryo-EM structure of TRPM1 reveals a canonical tetrameric fold in the intracellular domain but a non-canonical, inverted transmembrane domain arrangement: the voltage sensor-like domain (VSLD) and pore domain (PD) are domain-swapped with opposite handedness compared to other related channels, forming a large pore-like structure consistent with ion channel function. Cryogenic electron microscopy (cryo-EM) structural determination of purified TRPM1 Nature communications High 41857038
2026 Cryo-EM structure of human TRPM1 in conducting state reveals tetrameric assembly with an inverted (clockwise) domain-swapped pore module, dilated selectivity filter, expanded central cavity, and splayed S6 forming a wide intracellular gate. Single-channel recordings confirm constitutive activity consistent with the conductive state captured. Cryo-EM structural determination, single-channel electrophysiology bioRxiv (preprint)preprint Medium 41757028
2025 The IG domain of LRIT3 is required for localization of TRPM1 to the DBC signalplex; restoring LRIT3 lacking the IG domain fails to restore TRPM1 expression at synapses even when Nyctalopin is correctly localized. A model is proposed where the LRIT3 LRR domain trans-synaptically binds Nyctalopin while the IG domain interacts with TRPM1. rAAV-expressed LRIT3 deletion constructs in Lrit3-/- retina, immunofluorescence of TRPM1 and signalplex components, ERG bioRxiv (preprint)preprint Medium 41757028

Source papers

Stage 0 corpus · 89 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 263 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 248 19966281
2009 TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness. American journal of human genetics 187 19896113
2009 Mutations in TRPM1 are a common cause of complete congenital stationary night blindness. American journal of human genetics 183 19896109
2009 TRPM1 forms ion channels associated with melanin content in melanocytes. Science signaling 160 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 152 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 101 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 90 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 82 21832182
1998 Chromosomal localization and genomic characterization of the mouse melastatin gene (Mlsn1). Genomics 82 9806836
2011 Identification of autoantibodies against TRPM1 in patients with paraneoplastic retinopathy associated with ON bipolar cell dysfunction. PloS one 76 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 72 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 69 22586107
2011 Transient receptor potential melastatin 1 (TRPM1) is an ion-conducting plasma membrane channel inhibited by zinc ions. The Journal of biological chemistry 66 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 63 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 53 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 50 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
2019 Presynaptic Expression of LRIT3 Transsynaptically Organizes the Postsynaptic Glutamate Signaling Complex Containing TRPM1. Cell reports 44 31189098
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
2012 Depolarizing bipolar cell dysfunction due to a Trpm1 point mutation. Journal of neurophysiology 41 22896717
2013 Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes. Pigment cell & melanoma research 37 23452348
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
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 35 31985026
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
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 30 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 27 31743468
2011 Ultrastructural localization and expression of TRPM1 in the human retina. Investigative ophthalmology & visual science 26 21896854
2022 TRPM1 promotes tumor progression in acral melanoma by activating the Ca2+/CaMKIIδ/AKT pathway. Journal of advanced research 25 36585114
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
2019 TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations. Scientific reports 22 31427709
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 20 32386465
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
2018 Different Activity Patterns in Retinal Ganglion Cells of TRPM1 and mGluR6 Knockout Mice. BioMed research international 15 29854741
2019 TRPM1 Autoantibodies in Melanoma Patients Without Self-Reported Visual Symptoms. Investigative ophthalmology & visual science 14 31117125
2010 Plasticity of TRPM1 expression and localization in the wild type and degenerating mouse retina. Vision research 14 20801142
2022 Clinical and genetic findings in TRPM1-related congenital stationary night blindness. Acta ophthalmologica 11 35633130
2014 Choroidal atrophy in a patient with paraneoplastic retinopathy and anti-TRPM1 antibody. Clinical ophthalmology (Auckland, N.Z.) 11 24523577
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
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 9 27803854
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
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
2021 Trpm1: Novel function at the intersection of light and pain response in the iris. Experimental eye research 3 34954202
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
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
2026 Mutation Screening of ARR3, CACNA1F, P4HA2, TRPM1, COL2A1, COL11A1 and PAX6 in a Chinese Cohort of 37 Patients with Early-Onset High Myopia. Genes 0 42074509

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