Affinage

TRPC1

Short transient receptor potential channel 1 · UniProt P48995

Length
793 aa
Mass
91.2 kDa
Annotated
2026-04-28
100 papers in source corpus 43 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRPC1 is a non-selective, Ca²⁺-permeable cation channel subunit that does not form functional homomeric channels but assembles into heteromeric complexes with TRPC3/4/5/7, TRPP2, and TRPV4 to mediate store-operated and receptor-operated Ca²⁺ entry across diverse cell types (PMID:22157757, PMID:18323855, PMID:25114176). TRPC1 is gated by STIM1 via electrostatic interaction between STIM1 K684/K685 and TRPC1 D639/D640, with prior Orai1-mediated Ca²⁺ entry required for TRPC1 plasma membrane insertion; once at the surface, TRPC1 forms a ternary complex with STIM1 and Orai1 that generates Ca²⁺ signals distinct from Orai1 alone, selectively activating KCa channels and NFκB (PMID:21408196, PMID:18326500). Scaffolding by caveolin-1/caveolin-3 and α1-syntrophin anchors TRPC1 in membrane microdomains essential for its coupling to IP3 receptors, the dystrophin-associated protein complex, and downstream signaling including a Gαq–PLCβ1–PKC gating pathway (PMID:19052258, PMID:23203809, PMID:19812031, PMID:27753095). Through these spatially compartmentalized Ca²⁺ signals, TRPC1 controls skeletal myoblast migration via calpain-mediated MARCKS cleavage, mGluR-dependent synaptic plasticity and spatial working memory in hippocampal circuits, salivary gland fluid secretion, IFNγ-driven macrophage M1 polarization, and endothelial permeability (PMID:19001499, PMID:28790178, PMID:30271326, PMID:23203809, PMID:30293012, PMID:15920022).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Establishing that TRPC1 physically associates with polycystin-2 (PKD2) through two distinct domains revealed TRPC1 as a heteromeric channel partner capable of interacting with non-TRPC TRP family members.

    Evidence In vitro binding and co-IP with domain-mapping deletion mutants in transfected cells

    PMID:10097141

    Open questions at the time
    • Functional consequences of the PKD2–TRPC1 interaction on channel conductance were not yet determined
    • Stoichiometry of the complex was not resolved
  2. 2003 High

    Demonstrating that TRPC1 mediates the mGluR1-evoked slow EPSC in Purkinje cells and can be reconstituted with mGluR1 in heterologous systems established a physiological role for TRPC1 as a postsynaptic receptor-operated channel in the brain.

    Evidence Co-IP of native mGluR1–TRPC1 complex, antisense knockdown, and heterologous reconstitution with electrophysiology in Purkinje cells

    PMID:14614461

    Open questions at the time
    • Subunit composition of the native channel was not fully defined
    • Whether other TRPC subunits contribute to the slow EPSC was unresolved
  3. 2004 High

    Systematic topology mapping of human TRPC1 defined a six-transmembrane architecture with a pore-forming loop, providing the structural framework for understanding how TRPC1 contributes to ion permeation in heteromeric channels.

    Evidence Glycosylation-tagging topology assay with truncation mutant chimeras in HEK-293T cells

    PMID:14707123

    Open questions at the time
    • No high-resolution 3D structure was available
    • The exact pore-lining residues were not identified
  4. 2005 High

    Identification of endogenous TRPC1/TRPC3/TRPC7 trimeric complexes whose individual or combined knockdown ablated SOCE demonstrated that native store-operated channels are heteromeric assemblies requiring TRPC1.

    Evidence Reciprocal co-IP and combinatorial siRNA with Ba²⁺ entry assays in HEK-293 cells

    PMID:15972814

    Open questions at the time
    • How the trimer assembles and what dictates stoichiometry was unknown
    • Relationship to STIM1/Orai1 machinery was not yet addressed
  5. 2005 High

    Showing that angiopoietin-1 blocks VEGF-induced Ca²⁺ entry by disrupting IP3R–TRPC1 conformational coupling linked TRPC1 to regulation of endothelial permeability.

    Evidence Co-IP of IP3R–TRPC1, anti-TRPC1 antibody blockade, transendothelial resistance measurements

    PMID:15920022

    Open questions at the time
    • Whether IP3R–TRPC1 coupling is direct or via intermediary scaffolds was not resolved
  6. 2006 High

    Discovery that the STIM1 C-terminus directly binds and gates TRPC1 (but not TRPC3/6/7) via a lysine-rich region established STIM1 as the ER Ca²⁺ sensor that activates TRPC1 upon store depletion.

    Evidence Co-IP, siRNA, dominant-negative mutants, heterologous electrophysiology in HEK293 cells

    PMID:16906149

    Open questions at the time
    • Precise residues mediating the electrostatic interaction were not yet mapped
    • Role of Orai1 in the activation cascade was unaddressed
  7. 2008 High

    Multiple studies converged to show that TRPC1 assembles into heteromeric channels with TRPP2 (generating unique conductance properties), that caveolin-1/3 scaffolds TRPC1 at the plasma membrane, and that functional Orai1 is required for TRPC1-STIM1 store-operated entry, establishing the ternary Orai1/TRPC1/STIM1 complex.

    Evidence FRET (caveolin-3–TRPC1), co-IP from kidney and salivary gland, dominant-negative Orai1 pore mutants, patch clamp, Ca²⁺ imaging

    PMID:18323855 PMID:18326500 PMID:18544631 PMID:19052258

    Open questions at the time
    • How Orai1-mediated Ca²⁺ entry triggers TRPC1 trafficking to the plasma membrane was mechanistically unclear
    • Whether caveolin scaffolding is required in all cell types was not tested
  8. 2009 High

    Electrostatic gating of TRPC1 by STIM1 was mapped to specific residues (STIM1 K684/K685 ↔ TRPC1 D639/D640), α1-syntrophin was identified as a PDZ-domain anchor linking TRPC1/TRPC4 to the dystrophin complex, and TRPC1-mediated SOCE was shown to drive calpain/MARCKS-dependent myoblast migration.

    Evidence Pore-dead TRPC1(F562A) rescue, charge-swap mutagenesis, co-IP with PDZ-domain deletions, siRNA plus wound-healing assays in myoblasts

    PMID:19001499 PMID:19228695 PMID:19812031

    Open questions at the time
    • Structural basis for STIM1–TRPC1 gating complex was not determined
    • Whether α1-syntrophin anchoring is required for STIM1-mediated gating was not tested
  9. 2011 High

    Demonstration that Orai1-mediated Ca²⁺ entry is the prerequisite for TRPC1 plasma membrane insertion, after which STIM1 gates TRPC1, resolved the sequential activation model and showed that TRPC1 and Orai1 generate functionally distinct Ca²⁺ signals (TRPC1 → KCa/NFκB; Orai1 → NFAT).

    Evidence Surface biotinylation, dominant-negative Orai1, shRNA, patch clamp, live imaging in salivary gland cells

    PMID:21408196

    Open questions at the time
    • The trafficking machinery mediating Orai1-dependent TRPC1 insertion was not identified
    • Whether this sequential model applies universally across tissues was not established
  10. 2012 High

    Caveolin-1 knockout disrupted TRPC1–STIM1 interaction and fluid secretion in salivary glands (rescuable by Cav1 re-expression), while TRPC1 heteromerization with TRPC3/4/5/6/7 was shown to reduce pore Ca²⁺ permeability, establishing TRPC1 as a pore-contributing subunit that tunes selectivity of the heteromeric channel.

    Evidence Cav1 KO mice with adenoviral rescue, co-IP, pore-region mutagenesis, patch clamp in GnRH neurons

    PMID:22157757 PMID:23203809

    Open questions at the time
    • Cryo-EM or crystal structure of a TRPC1-containing heteromer was lacking
    • How TRPC1 incorporation changes pore geometry at atomic level was unknown
  11. 2014 High

    TRPC1 was found to participate in a cross-subfamily heteromeric channel with TRPV4 and TRPP2 (all three contributing to the pore), and separately, caspase-11 was identified as cleaving TRPC1 to regulate IL-1β secretion in macrophages, revealing a non-canonical role in innate immunity.

    Evidence Two-step co-IP, FRET, pore-dead mutants in endothelial cells; caspase-11 cleavage assay, TRPC1 KO mice with LPS peritonitis model

    PMID:24630989 PMID:25114176

    Open questions at the time
    • How caspase-11 accesses TRPC1 and whether cleavage products retain channel function was unresolved
    • Stoichiometry of the TRPV4/TRPC1/TRPP2 trimeric channel was not determined
  12. 2015 High

    A Gαq–PLCβ1–PKC signaling axis was shown to gate TRPC1-based SOCs downstream of STIM1 in vascular smooth muscle, and separately, TRPC1/Orai1/STIM1 ternary complexes were demonstrated to regulate glucose-stimulated insulin secretion in β-cells.

    Evidence PLA, GFP-PLCδ1-PH biosensor, PLCβ1 shRNA, patch clamp in VSMCs; pore-mutant dominants and insulin secretion assay in β-cells

    PMID:26467792 PMID:26494622 PMID:27753095

    Open questions at the time
    • PKC phosphorylation site(s) on TRPC1 were not mapped
    • Whether the Gαq–PLCβ1 gating mechanism operates in non-muscle cells was unclear
  13. 2017 High

    Quantitative mass spectrometry and triple-KO mice established TRPC1/4/5 heteromers as the native hippocampal channel supporting mGluR5-dependent synaptic plasticity (LTP, LTD) and spatial working memory, while Pico145 provided the first high-potency pharmacological tool selective for TRPC1/4/5 subtypes.

    Evidence Quantitative MS from mouse brain, Trpc1/4/5 triple KO with slice electrophysiology and behavioral assays, Pico145 electrophysiology profiling

    PMID:28325835 PMID:28790178 PMID:30271326

    Open questions at the time
    • Whether TRPC1/4/5 channels are presynaptic, postsynaptic, or both was not fully resolved
    • The specific Ca²⁺-dependent effectors downstream of TRPC1/4/5 in LTP/LTD were not identified
  14. 2018 Medium

    TRPC1 was identified as necessary for IFNγ-induced M1 macrophage polarization, with TRPC1⁻/⁻ macrophages showing abrogated inflammatory mediator production both in vitro and in a Klebsiella peritonitis model.

    Evidence TRPC1⁻/⁻ mice, macrophage polarization assays, Ca²⁺ imaging, in vivo infection model

    PMID:30293012

    Open questions at the time
    • The Ca²⁺-dependent signaling pathway linking TRPC1 to M1 gene transcription was not delineated
    • Single lab finding awaits independent replication
  15. 2020 High

    HSV-1 glycoprotein D was shown to directly bind the third ectodomain of TRPC1 to facilitate viral entry and Ca²⁺ influx, establishing TRPC1 as a virus entry receptor.

    Evidence Co-IP of gD–TRPC1, ectodomain mapping, TRPC1⁻/⁻ mice with attenuated viral entry and ocular pathology

    PMID:32206724

    Open questions at the time
    • Whether TRPC1 channel activity versus surface expression is the determinant for viral entry was not distinguished
    • Structural basis of gD–TRPC1 ectodomain interaction was not solved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of a TRPC1-containing heteromeric channel, the precise trafficking machinery linking Orai1-mediated Ca²⁺ to TRPC1 plasma membrane insertion, the identity of PKC phosphorylation sites on TRPC1, and whether TRPC1's scaffolding (channel-independent) function contributes to its physiological roles in vivo.
  • No cryo-EM or crystal structure of any TRPC1-containing heteromer
  • Trafficking machinery for Ca²⁺-dependent TRPC1 insertion unidentified
  • Channel-independent scaffolding roles demonstrated in PC12 cells but not validated in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-112316 Neuronal System 3 R-HSA-382551 Transport of small molecules 3 R-HSA-168256 Immune System 2
Complex memberships
Dystrophin-associated protein complex (DAPC)Orai1/TRPC1/STIM1 ternary complexTRPC1/TRPC4/TRPC5 heteromeric channelTRPV4/TRPC1/TRPP2 heteromeric channel

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 The cytosolic C-terminus of STIM1 directly binds and activates TRPC1 (but not TRPC3, 6, or 7) via its ERM domain, with selective binding to TRPC1/2/4; a cationic lysine-rich region of STIM1 is required for gating of TRPC1. The STIM1 C-terminus is sufficient to activate TRPC1 channels even when endogenous STIM1 is depleted. Co-immunoprecipitation, siRNA knockdown, dominant-negative mutants, heterologous expression in HEK293 cells, electrophysiology Nature cell biology High 16906149
2003 TRPC1 mediates the mGluR1-evoked slow excitatory postsynaptic conductance in cerebellar Purkinje cells. TRPC1 is physically associated with mGluR1 at the perisynaptic region, and co-expression of mGluR1 and TRPC1 in a heterologous system reconstitutes an mGluR1-evoked conductance resembling the slow EPSC. Co-immunoprecipitation, heterologous reconstitution, antisense oligonucleotide knockdown, electrophysiology in Purkinje cells Nature High 14614461
1999 PKD2 (polycystin-2) directly associates with TRPC1 but not TRPC3 via two distinct domains: a 73-amino-acid region in the C-terminal cytoplasmic tail of PKD2 and a transmembrane domain (S2–S5) including the pore helix region. Co-immunoprecipitation in transfected cells and in vitro binding assays, domain mapping with deletion mutants Proceedings of the National Academy of Sciences High 10097141
2008 TRPP2 and TRPC1 assemble as an intergroup heteromeric channel with unique conductance, amiloride sensitivity, and ion permeability distinct from either subunit alone; activated by G-protein-coupled receptor stimulation. Native TRPP2/TRPC1 activity demonstrated in kidney cells by co-immunoprecipitation and co-localization at the primary cilium. Co-immunoprecipitation from kidney membranes, gain/loss-of-function electrophysiology, immunolocalization, patch clamp EMBO reports High 18323855
2011 Ca2+ entry via Orai1 is required to trigger plasma membrane insertion (trafficking) of TRPC1; once at the plasma membrane, TRPC1 is gated by STIM1 via electrostatic interaction (STIM1 K684/K685 with TRPC1 D639/D640). Orai1 and TRPC1 form discrete STIM1-gated channels generating distinct Ca2+ signals regulating different cellular functions (TRPC1 required for KCa activity and NFκB, Orai1 sufficient for NFAT). Dominant-negative Orai1 mutants, shRNA knockdown, Ca2+ imaging, patch clamp, surface biotinylation, live imaging PLoS biology High 21408196
2008 Functional Orai1 (channel function) is required for TRPC1+STIM1-dependent store-operated Ca2+ entry and ISOC current in HEK293 cells. Endogenous TRPC1, STIM1, and Orai1 co-immunoprecipitate from salivary glands, forming a ternary complex. siRNA knockdown, dominant-negative Orai1 pore mutants (R91W, E106Q), co-immunoprecipitation, Ca2+ imaging, patch clamp Journal of Biological Chemistry High 18326500
2009 Native store-operated Ca2+ channels in HEK cells require both Orai1 and TRPC1 channel functions; pore-dead TRPC1(F562A) fails to rescue SOC activity, and TRPC1 gating involves electrostatic interaction between TRPC1(D639/D640) and STIM1(K684/K685). Orai1 and TRPC1 mutually require each other for interaction with STIM1. siRNA knockdown, siRNA-resistant mutant rescue, pore mutants, co-immunoprecipitation, Ca2+ imaging, electrophysiology Journal of Biological Chemistry High 19228695
2005 Endogenous TRPC1, TRPC3, and TRPC7 form heteromeric store-operated channels in HEK-293 cells, as shown by co-immunoprecipitation of the trimeric complex; individual or combined siRNA suppression inhibits SOCE. siRNA knockdown (individual and combined), co-immunoprecipitation, Ca2+ imaging (Ba2+ entry assay) Journal of Biological Chemistry High 15972814
2008 TRPC1 physically associates with caveolin-3 at the plasma membrane of muscle cells (confirmed by FRET between TRPC1-CFP and caveolin-3-YFP). Caveolin-3 targets TRPC1 to the plasma membrane. ROS-activated Src kinase enhances Ca2+ influx through the TRPC1/caveolin-3 complex, contributing to mdx/DMD pathogenesis. FRET, co-immunoprecipitation, confocal microscopy, pharmacological inhibition (PP2, Tiron), Ca2+ imaging in C2 myoblasts and mdx muscle Journal of cell science High 18544631
2011 TRPC1 does not form functional homomeric channels when expressed alone; instead it assembles into heteromeric receptor-operated channels with TRPC3, 4, 5, 6, or 7. Incorporation of TRPC1 into heteromers significantly reduces calcium permeability, and pore-region mutations in TRPC1 further reduce calcium permeability, demonstrating TRPC1 contributes to the channel pore. Electrophysiology (patch clamp), Ca2+ imaging, site-directed mutagenesis of pore region, siRNA knockdown in GnRH neurons Journal of Biological Chemistry High 22157757
2014 TRPV4, TRPC1, and TRPP2 assemble into a heteromeric channel complex in rat mesenteric artery endothelial cells; pore-dead mutants of each subunit nearly abolish flow-induced cation currents, indicating all three contribute to the ion permeation pore of a cross-subfamily TRP channel. Two-step co-immunoprecipitation, FRET, patch clamp, Ca2+ imaging, pore-dead mutants FASEB journal High 25114176
2005 Angiopoietin-1 inhibits VEGF-induced Ca2+ influx through TRPC1 by interfering with the interaction between IP3 receptor (IP3R) and TRPC1, thereby blocking the conformational coupling mechanism of Ca2+ entry and abrogating increased endothelial permeability. Co-immunoprecipitation (IP3R–TRPC1), anti-TRPC1 antibody blockade, TRPC1 overexpression, Ca2+ imaging, transendothelial resistance measurements Circulation research High 15920022
2008 Caveolin-1 scaffold domain (CSD, residues 82–101) directly interacts with TRPC1 C-terminal residues 781–789 and with IP3R3; this interaction is required for Ca2+ store release-induced Ca2+ influx. Loss of either TRPC1 C-terminal CSD-binding domain or the CSD itself disrupts TRPC1-IP3R3 interaction and abolishes Ca2+ entry. Co-immunoprecipitation, truncation/deletion mutants, Ca2+ imaging, confocal microscopy in HMEC and HEK-293 cells American Journal of Physiology. Cell physiology High 19052258
2017 TRPC1, TRPC4, and TRPC5 assemble into heteromultimers with each other (but not other TRP family members) in mouse brain/hippocampus, as shown by quantitative mass spectrometry. These heteromeric channels facilitate action potential-triggered EPSCs and support hippocampal spatial working memory and synaptic transmission. Quantitative high-resolution mass spectrometry, triple knockout mice, electrophysiology (evoked EPSCs, LTP), in vivo hippocampal recordings, behavioral assays EMBO journal High 28790178
2004 Human TRPC1 has a six-transmembrane topology where HRs 1, 4, and 6 cross from cytosol to ER lumen, HRs 2, 5, and 8 have opposite orientation, HR 3 remains cytosolic, and HR 7 forms a pore-like structure stabilized by the sequence downstream of HR 8 anchoring the C-terminal end on the cytosolic side. Truncation mutant chimeras fused to eGFP with C-terminal glycosylation tags, glycosylation topology assay in HEK-293T cells Journal of Biological Chemistry High 14707123
2009 TRPC1 regulates skeletal myoblast migration by mediating store-operated Ca2+ entry that activates calpain, which cleaves MARCKS (an actin-binding protein), thereby enabling cytoskeletal rearrangement, cell migration, and fusion into myotubes. siRNA knockdown of TRPC1, calpain activity assay, MARCKS immunoblotting, Ca2+ imaging, wound-healing migration assay, GsMTx4 and calpain inhibitor pharmacology, IGF-1 stimulation Journal of cell science High 19001499
2009 TRPC1 operates as a sarcoplasmic reticulum Ca2+ leak channel in skeletal muscle fibers (not a sarcolemmal channel); overexpressed TRPC1-YFP co-localizes with SR Ca2+ pump markers and elevates resting SR Ca2+ and the rate of Ca2+ leak upon SR pump inhibition. Overexpression of TRPC1-YFP in adult mouse muscle fibers, immunostaining co-localization, Ca2+ imaging, cyclopiazonic acid SR depletion, voltage clamp Journal of Biological Chemistry Medium 19875453
2009 TRPC1 and TRPC3 are co-immunoprecipitated from vascular smooth muscle cells and are inhibited by NO via a PKG-dependent mechanism (cGMP/PKG pathway), contributing to NO-mediated vasorelaxation. Co-immunoprecipitation, patch clamp (whole-cell), PKG inhibitor (KT5823), NO donor, vessel myograph American Journal of Physiology. Heart and circulatory physiology Medium 19502552
2009 TRPC1 channels require α1-syntrophin (via its PDZ domain) for proper sarcolemmal localization and normal cation influx in skeletal myotubes. TRPC1 and TRPC4 form channels anchored to the dystrophin-associated protein complex (DAPC) through α1-syntrophin, regulating cation entry. siRNA knockdown of α1-syntrophin, co-immunoprecipitation, forced expression with PDZ-domain deletion constructs, Ca2+ imaging Journal of Biological Chemistry High 19812031
2014 Caspase-11 cleaves/degrades TRPC1 as a substrate; TRPC1 deficiency increases IL-1β secretion in macrophages and in a sepsis model, identifying TRPC1 as a negative regulator of unconventional IL-1β secretion in a caspase-1-independent manner. Caspase-11 cleavage assay, TRPC1 KO mice, LPS-induced peritonitis model, IL-1β ELISA, caspase-1 cleavage assays Cell reports High 24630989
2012 Caveolin-1 is required for assembly of functional TRPC1 channels in salivary glands; Cav1 knockout disrupts microdomain localization of TRPC1 and its interaction with STIM1 (but not Orai1-STIM1 interaction), reducing agonist-stimulated Ca2+ entry and fluid secretion. Re-expression of Cav1 restores TRPC1-STIM1 interaction and channel function. Caveolin-1 KO mice, adenoviral Cav1 rescue, co-immunoprecipitation, Ca2+ imaging, fluid secretion assay Journal of cell science High 23203809
2016 Store-operated interactions between plasma membrane STIM1 and TRPC1 activate PLCβ1 (via Gαq) and subsequent PKC phosphorylation of TRPC1, which gates the channel in vascular smooth muscle cells. STIM1 translocation to the PM upon store depletion forms STIM1-TRPC1-Gαq-PLCβ1 complexes. Patch clamp, co-immunoprecipitation, proximity ligation assay, GFP-PLCδ1-PH biosensor imaging, STIM1 shRNA, TRPC1−/− VSMCs, antibody inhibition Journal of Physiology High 27753095
2015 Store depletion induces TRPC1 to form complexes with Gαq and PLCβ1, with PLCβ1 activity (via Gαq) driving PKC-dependent phosphorylation and gating of TRPC1-based SOCs in vascular smooth muscle cells; PLCβ1 shRNA reduces both store-operated PLC activity and TRPC1 current. Patch clamp, GFP-PLCδ1-PH imaging, co-immunoprecipitation, PLCβ1 shRNA, pharmacological inhibitors (GDP-βS, U73122, GF109203X), Ca2+ store depletion FASEB journal High 26467792
2018 IFNγ-induced M1 macrophage polarization requires TRPC1-mediated Ca2+ entry; TRPC1−/− macrophages display abrogated IFNγ-induced M1 inflammatory mediators both in vitro and in a Klebsiella pneumoniae peritonitis model in vivo. TRPC1−/− mice, in vitro macrophage polarization assays, Ca2+ imaging, in vivo infection model, human patient TRPC1 expression correlation with M1 markers iScience Medium 30293012
2015 TRPC1 and Orai1 form functional store-operated Ca2+ channels regulated by STIM1 in pancreatic β-cells; store depletion induces assembly of an Orai1/TRPC1/STIM1 ternary complex, and dominant-negative pore mutants (Orai1-E106D, TRPC1-F562A) block SOCE and impair glucose-stimulated insulin secretion. Co-immunoprecipitation, pore-mutant dominant-negative expression, Ca2+ imaging, patch clamp, insulin secretion assay in rat β-cells Journal of Biological Chemistry High 26494622
2015 RhoA physically associates with TRPC1 in intestinal epithelial cells; RhoA activation increases the RhoA/TRPC1 complex, enhances store-operated Ca2+ entry, and promotes cell migration after wounding. Inhibition of RhoA or knockdown of TRPC1 reduces Ca2+ influx and epithelial restitution. Co-immunoprecipitation, dominant-negative and wild-type RhoA overexpression, siRNA, Ca2+ imaging, wound-healing assay American Journal of Physiology. Gastrointestinal and liver physiology Medium 26336927
2011 TRPC1-promoted neurite outgrowth in PC12 cells is independent of Ca2+ influx (channel-dead TRPC1 pore mutant promotes neurite outgrowth equally to wild-type); TRPC1 likely acts as a scaffold at the cell surface to assemble a signaling complex. TRPC5 suppresses TRPC1-induced neurite outgrowth by reducing TRPC1 surface expression. Channel-dead pore mutant expression, Ca2+ imaging, neurite length quantification, surface expression analysis, TRPC1/TRPC5 co-expression Cellular signalling Medium 22201561
2012 TRPC1 knockdown in non-small cell lung carcinoma cells causes G0/G1 arrest and reduces EGFR phosphorylation and downstream PI3K/Akt and MAPK signaling. EGF-induced Ca2+ entry through TRPC1 activates EGFR in a positive feedback loop. siRNA knockdown, Ca2+ imaging, cell cycle analysis, immunoblotting of EGFR phosphorylation and downstream signaling Journal of Biological Chemistry Medium 22451676
2020 HSV-1 glycoprotein D directly interacts with the third ectodomain of TRPC1, facilitating viral entry. TRPC1 knockout attenuates HSV-1-induced Ca2+ entry, viral entry, and ocular pathology in mice. Co-immunoprecipitation (gD–TRPC1), TRPC1−/− mice, Ca2+ imaging, viral entry assays, ectodomain mapping Science advances High 32206724
2017 mGluR5 activates TRPC1-containing channels (TRPC1/4/5 complexes) in hippocampal CA1-3 neurons; Trpc1 knockout mice show impaired mGluR5-induced cation entry, disrupted LTP maintenance, impaired mGluR-LTD, and spatial working memory deficits. Acute inhibition with Pico145 mimics genetic depletion. Trpc1 knockout mice, patch clamp in brain slices, LTP/LTD electrophysiology, Pico145 pharmacology, behavioral memory assays Frontiers in cellular neuroscience High 30271326
2006 NRSF (neuron-restrictive silencer factor) binds a neuron-restrictive silencer element-like sequence in intron 4 of the TRPC1 gene and represses TRPC1 transcription; dominant-negative NRSF upregulates TRPC1, leading to increased NFAT promoter activity and store-operated Ca2+ entry. EMSA (NRSF binding to TRPC1 intronic sequence), RT-PCR/Western in dnNRSF transgenic mice, NFAT-luciferase reporter, Ca2+ imaging Biochemical and biophysical research communications Medium 17084381
2011 The actin and microtubular cytoskeleton modulate SOCE by regulating physical association between STIM1 and TRPC1 (and Orai1); microtubule disruption (colchicine) enhances STIM1–TRPC1 association and SOCE, while microtubule stabilization (paclitaxel) or cortical actin stabilization reduces these interactions. Co-immunoprecipitation (STIM1–TRPC1/Orai1), cytoskeletal pharmacology (colchicine, paclitaxel, cytochalasin D), Ca2+ imaging in HEK-293 cells Biochemical pharmacology Medium 21640715
2016 SARAF (SOCE-associated regulatory factor) interacts with TRPC1 independently of STIM1 and negatively regulates TRPC1-mediated Ca2+ entry; agonist (ATP) stimulation enhances SARAF–TRPC1 interaction. SARAF does not regulate TRPC6 in the same manner. Co-immunoprecipitation in STIM1-deficient and STIM1-expressing cells, SARAF siRNA knockdown, Ca2+ imaging Biochemical journal Medium 27506849
2012 TRPC1 and Orai1 interact with STIM1 and mediate capacitative Ca2+ entry caused by acute hypoxia in mouse pulmonary arterial smooth muscle cells; hypoxia increases co-immunoprecipitation of TRPC1-STIM1 and Orai1-STIM1 complexes, and siRNA knockdown of any component inhibits the hypoxia-induced Ca2+ rise. siRNA knockdown (TRPC1, STIM1, Orai1), co-immunoprecipitation, immunostaining, Ca2+ imaging (fura-2, Mn2+ quench), patch clamp American Journal of Physiology. Cell physiology Medium 23034388
2021 TRPC1 directly binds calmodulin (CaM) and enhances the interaction between CaM and the PI3K p85 subunit, thereby activating PI3K/AKT and downstream cell cycle and EMT signaling pathways in colorectal cancer; CaM silencing abrogates TRPC1 oncogenic effects. Co-immunoprecipitation (TRPC1–CaM, CaM–PI3K p85), TRPC1 KO mice, siRNA knockdown, in vivo tumor models, cell cycle analysis, immunoblotting Oncogenesis Medium 34642309
2017 TRPC4 and TRPC5 form heteromeric channels with TRPC1; TRPC1/4/5 subtype-specific compound Pico145 inhibits these channels at picomolar concentrations, with potency ranging from 9 to 1300 pM depending on subtype and activation mechanism, while TRPC3, TRPC6, and other TRP channels are unaffected. Ca2+ assays and patch clamp electrophysiology on native and overexpressed channels; chemical synthesis and structure-activity relationship Journal of Biological Chemistry High 28325835
2014 TRPC1 and TRPC4 are upregulated in bladder-innervating sensory neurons during cystitis; TRPC1/TRPC4 double knockout mice fail to develop cyclophosphamide-induced sensory fiber sprouting and show diminished bladder overactivity. TRPC1/TRPC4 double KO mice, quantitative RT-PCR, immunohistochemistry, urodynamic analysis, detrusor strip contractility PLoS one Medium 23922735
2012 TRPC1 mediates Ca2+ influx that activates protein phosphatase 2A (PP2A), which in turn inhibits NF-κB activation and sensitizes intestinal epithelial cells to apoptosis; okadaic acid (PP2A inhibitor) or PP2A siRNA rescues NF-κB activity and prevents apoptosis in TRPC1-overexpressing cells. Stable TRPC1 transfection, PP2A siRNA, okadaic acid, NF-κB luciferase reporter, apoptosis assays, Ca2+ imaging American Journal of Physiology. Cell physiology Medium 18322138
2017 TRPC1 and TRPC4 functionally interact with STIM1L (muscle-specific long STIM1 isoform) preferentially over STIM1 upon store depletion in human myotubes, contributing to ~50% of SOCE and supporting myoblast differentiation; STIM1L or TRPC1/4 knockdown each delay myogenesis similarly. siRNA knockdown (TRPC1, TRPC4, STIM1L), co-immunoprecipitation, Ca2+ imaging, differentiation index measurement Biochimica et biophysica acta. Molecular cell research Medium 28185894
2016 Sphingosine-1-phosphate (S1P) activates TRPC1 channel in glioblastoma cells; PDGF-induced Ca2+ entry via TRPC1 is mediated through sphingosine kinase/S1P, and TRPC1 translocates to the leading edge (lamellipodia) in a PI3K-dependent manner during chemotaxis. siRNA knockdown, SKI-II (sphingosine kinase inhibitor), LY294002 (PI3K inhibitor), Ca2+ imaging, immunocytochemistry of TRPC1 localization, chemotaxis assay Cell calcium Medium 27638096
2022 TRPC1 channels mediate tensile-strain-induced Ca2+ responses in mouse Müller glia cells; pharmacological inhibition and knockdown of TRPC1 reduce stretch-evoked Ca2+ increases, acting synergistically with TRPV4. Trpc1 knockdown, pharmacological inhibition, cyclic radial substrate deformation, Ca2+ imaging with indicator dye, TRPV4 KO comparison Cell calcium Medium 35398674
2008 HNF4α transcription factor directly binds to a regulatory region in the TRPC1 gene (identified by chromatin immunoprecipitation) and controls TRPC1 expression in kidney; siRNA knockdown of HNF4α reduces TRPC1 expression in cell culture. Chromatin immunoprecipitation-cloning, siRNA knockdown of HNF4α, RT-PCR, Western blot in diabetic rat models Diabetes Medium 18184923
2003 TNF-α induces TRPC1 expression in human endothelial cells through an NF-κB-dependent pathway; the TRPC1 promoter contains four NF-κB binding sites, and kinase-dead IKKβ, non-phosphorylatable IκBα mutant, or NEMO-binding domain peptide each block TNF-α-induced TRPC1 expression and the resulting augmented Ca2+ entry. TRPC1 promoter-luciferase reporter, dominant-negative IKKβ and IκBα constructs, NEMO-binding peptide, RT-PCR, Western blot, Ca2+ imaging Journal of Biological Chemistry Medium 12855710

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels. Nature cell biology 538 16906149
2003 Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1. Nature 284 14614461
1999 Specific association of the gene product of PKD2 with the TRPC1 channel. Proceedings of the National Academy of Sciences of the United States of America 260 10097141
2007 Revisiting TRPC1 and TRPC6 mechanosensitivity. Pflugers Archiv : European journal of physiology 216 17957383
2011 Local Ca²+ entry via Orai1 regulates plasma membrane recruitment of TRPC1 and controls cytosolic Ca²+ signals required for specific cell functions. PLoS biology 210 21408196
2016 TRPC1, Orai1, and STIM1 in SOCE: Friends in tight spaces. Cell calcium 184 28089266
2008 Functional requirement for Orai1 in store-operated TRPC1-STIM1 channels. The Journal of biological chemistry 182 18326500
2005 Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells. The Journal of biological chemistry 172 15972814
2009 TRPC1 and TRPC6 channels cooperate with TRPV4 to mediate mechanical hyperalgesia and nociceptor sensitization. The Journal of neuroscience : the official journal of the Society for Neuroscience 171 19439599
2006 Upregulation of TRPC1 in the development of cardiac hypertrophy. Journal of molecular and cellular cardiology 164 17174323
2005 Angiopoietin-1 opposes VEGF-induced increase in endothelial permeability by inhibiting TRPC1-dependent Ca2 influx. Circulation research 143 15920022
2008 TRPC1 binds to caveolin-3 and is regulated by Src kinase - role in Duchenne muscular dystrophy. Journal of cell science 135 18544631
2005 TRPC1: store-operated channel and more. Pflugers Archiv : European journal of physiology 134 15965706
2008 Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and TRPC1 subunits. EMBO reports 133 18323855
2004 Tumor necrosis factor-alpha-induced TRPC1 expression amplifies store-operated Ca2+ influx and endothelial permeability. American journal of physiology. Lung cellular and molecular physiology 131 15347566
2009 Native Store-operated Ca2+ Influx Requires the Channel Function of Orai1 and TRPC1. The Journal of biological chemistry 129 19228695
2008 TRPC1 regulates skeletal myoblast migration and differentiation. Journal of cell science 127 19001499
2011 Transient receptor potential channel 1 (TRPC1) reduces calcium permeability in heteromeric channel complexes. The Journal of biological chemistry 123 22157757
2014 MiR-135a promotes renal fibrosis in diabetic nephropathy by regulating TRPC1. Diabetologia 117 24908566
2017 Heteromeric channels formed by TRPC1, TRPC4 and TRPC5 define hippocampal synaptic transmission and working memory. The EMBO journal 107 28790178
2014 TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 100 25114176
2004 Overexpression of TRPC1 enhances pulmonary vasoconstriction induced by capacitative Ca2+ entry. American journal of physiology. Lung cellular and molecular physiology 100 15220115
2008 Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells. American journal of physiology. Cell physiology 99 19052258
2008 Store-operated Ca2+ channels formed by TRPC1, TRPC6 and Orai1 and non-store-operated channels formed by TRPC3 are involved in the regulation of NADPH oxidase in HL-60 granulocytes. Cell calcium 98 18436303
2017 Picomolar, selective, and subtype-specific small-molecule inhibition of TRPC1/4/5 channels. The Journal of biological chemistry 96 28325835
1998 Functional expression of TrpC1: a human homologue of the Drosophila Trp channel. The Biochemical journal 93 9512497
2004 TRPC1-mediated inhibition of 1-methyl-4-phenylpyridinium ion neurotoxicity in human SH-SY5Y neuroblastoma cells. The Journal of biological chemistry 89 15542611
2014 Caspase-11 controls interleukin-1β release through degradation of TRPC1. Cell reports 83 24630989
2003 Tumor necrosis factor-alpha induces nuclear factor-kappaB-dependent TRPC1 expression in endothelial cells. The Journal of biological chemistry 81 12855710
2012 TRPC1 protein channel is major regulator of epidermal growth factor receptor signaling. The Journal of biological chemistry 80 22451676
2017 TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells. Journal of cell science 79 28559303
2008 Interactions, functions, and independence of plasma membrane STIM1 and TRPC1 in vascular smooth muscle cells. Circulation research 79 18802022
2011 Contribution of TRPC1 and Orai1 to Ca(2+) entry activated by store depletion. Advances in experimental medicine and biology 75 21290310
2018 M1 Macrophage Polarization Is Dependent on TRPC1-Mediated Calcium Entry. iScience 73 30293012
2015 Store-operated Ca2+ Entry Mediated by Orai1 and TRPC1 Participates to Insulin Secretion in Rat β-Cells. The Journal of biological chemistry 73 26494622
2014 Classical Transient Receptor Potential 1 (TRPC1): Channel or Channel Regulator? Cells 71 25268281
2009 TRPC1 inhibits apoptotic cell degeneration induced by dopaminergic neurotoxin MPTP/MPP(+). Cell calcium 70 19695701
2018 Ca2+ handling remodeling and STIM1L/Orai1/TRPC1/TRPC4 upregulation in monocrotaline-induced right ventricular hypertrophy. Journal of molecular and cellular cardiology 64 29634917
2009 Inhibition of TRPC1/TRPC3 by PKG contributes to NO-mediated vasorelaxation. American journal of physiology. Heart and circulatory physiology 64 19502552
2020 The Role of TRPC1 in Modulating Cancer Progression. Cells 63 32046188
2009 Regulation of TRPC1 and TRPC4 cation channels requires an alpha1-syntrophin-dependent complex in skeletal mouse myotubes. The Journal of biological chemistry 63 19812031
2008 HNF4 alpha and the Ca-channel TRPC1 are novel disease candidate genes in diabetic nephropathy. Diabetes 57 18184923
2018 Activation of TRPC1 Channel by Metabotropic Glutamate Receptor mGluR5 Modulates Synaptic Plasticity and Spatial Working Memory. Frontiers in cellular neuroscience 56 30271326
2011 The dynamic complexity of the TRPC1 channelosome. Channels (Austin, Tex.) 53 21747233
2012 Impairment of TRPC1-STIM1 channel assembly and AQP5 translocation compromise agonist-stimulated fluid secretion in mice lacking caveolin1. Journal of cell science 52 23203809
2019 Ambient and supplemental magnetic fields promote myogenesis via a TRPC1-mitochondrial axis: evidence of a magnetic mitohormetic mechanism. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 50 31518158
2005 Evidence that TRPC1 contributes to calcium-induced differentiation of human keratinocytes. Pflugers Archiv : European journal of physiology 49 16283206
2011 The cytoskeleton plays a modulatory role in the association between STIM1 and the Ca2+ channel subunits Orai1 and TRPC1. Biochemical pharmacology 46 21640715
2016 Role of TRPC1 channels in pressure-mediated activation of murine pancreatic stellate cells. European biophysics journal : EBJ 45 27670661
2005 Distribution of TRPC1 and TRPC5 in medial temporal lobe structures of mice. Cell and tissue research 45 16044320
2009 Glucose enhances expression of TRPC1 and calcium entry in endothelial cells. American journal of physiology. Heart and circulatory physiology 44 19855058
2009 TRPC1 is regulated by caveolin-1 and is involved in oxidized LDL-induced apoptosis of vascular smooth muscle cells. Journal of cellular and molecular medicine 44 20187291
2009 Transient receptor potential canonical type 1 (TRPC1) operates as a sarcoplasmic reticulum calcium leak channel in skeletal muscle. The Journal of biological chemistry 43 19875453
2017 TRPC1 and TRPC4 channels functionally interact with STIM1L to promote myogenesis and maintain fast repetitive Ca2+ release in human myotubes. Biochimica et biophysica acta. Molecular cell research 42 28185894
2017 Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced nitric oxide production and vasorelaxation in rabbit mesenteric arteries. Vascular pharmacology 41 28867591
2014 TRPC1. Handbook of experimental pharmacology 41 24756701
2012 TRPC1 and Orai1 interact with STIM1 and mediate capacitative Ca(2+) entry caused by acute hypoxia in mouse pulmonary arterial smooth muscle cells. American journal of physiology. Cell physiology 41 23034388
2018 TRPC1/3/6 inhibition attenuates the TGF-β1-induced epithelial-mesenchymal transition in gastric cancer via the Ras/Raf1/ERK signaling pathway. Cell biology international 39 29570903
2016 Sphingosine-1-phosphate-activated TRPC1 channel controls chemotaxis of glioblastoma cells. Cell calcium 39 27638096
2012 Platelet-derived growth factor-BB restores human immunodeficiency virus Tat-cocaine-mediated impairment of neurogenesis: role of TRPC1 channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 39 22815499
2016 Orai1 and TRPC1 Proteins Co-localize with CaV1.2 Channels to Form a Signal Complex in Vascular Smooth Muscle Cells. The Journal of biological chemistry 38 27535226
2015 TRPC1-mediated Ca²⁺ entry is essential for the regulation of hypoxia and nutrient depletion-dependent autophagy. Cell death & disease 37 25741599
2012 Role of TRPC1 and TRPC3 channels in contraction and relaxation of mouse thoracic aorta. Journal of vascular research 37 23095462
2011 Opposite regulatory effects of TRPC1 and TRPC5 on neurite outgrowth in PC12 cells. Cellular signalling 37 22201561
2006 Induced TRPC1 expression sensitizes intestinal epithelial cells to apoptosis by inhibiting NF-kappaB activation through Ca2+ influx. The Biochemical journal 36 16551274
2019 Role of TRPC1 channels in pressure-mediated activation of airway remodeling. Respiratory research 35 31092255
2019 TRPC1 and ORAI1 channels in colon cancer. Cell calcium 34 31203007
2008 Evaluation of genetic association and expression reduction of TRPC1 in the development of diabetic nephropathy. American journal of nephrology 33 18802326
2019 TRPC1 as a negative regulator for TRPC4 and TRPC5 channels. Pflugers Archiv : European journal of physiology 32 31222490
2016 Store-operated interactions between plasmalemmal STIM1 and TRPC1 proteins stimulate PLCβ1 to induce TRPC1 channel activation in vascular smooth muscle cells. The Journal of physiology 32 27753095
2012 Silencing TRPC1 expression inhibits invasion of CNE2 nasopharyngeal tumor cells. Oncology reports 32 22367186
2023 The Molecular Heterogeneity of Store-Operated Ca2+ Entry in Vascular Endothelial Cells: The Different roles of Orai1 and TRPC1/TRPC4 Channels in the Transition from Ca2+-Selective to Non-Selective Cation Currents. International journal of molecular sciences 31 36834672
2011 Upregulated TRPC3 and Downregulated TRPC1 Channel Expression during Hypertension is Associated with Increased Vascular Contractility in Rat. Frontiers in physiology 31 21811471
2017 TRPC1 stimulates calcium‑sensing receptor‑induced store‑operated Ca2+ entry and nitric oxide production in endothelial cells. Molecular medicine reports 29 28791397
2015 RhoA enhances store-operated Ca2+ entry and intestinal epithelial restitution by interacting with TRPC1 after wounding. American journal of physiology. Gastrointestinal and liver physiology 29 26336927
2015 The contribution of TRPC1, TRPC3, TRPC5 and TRPC6 to touch and hearing. Neuroscience letters 29 26520460
2012 Critical role of TRPC1-mediated Ca²⁺ entry in decidualization of human endometrial stromal cells. Molecular endocrinology (Baltimore, Md.) 29 22474110
2007 Store-operated Orai1 and IP3 receptor-operated TRPC1 channel. Channels (Austin, Tex.) 29 18711860
2021 TRPC1 promotes the genesis and progression of colorectal cancer via activating CaM-mediated PI3K/AKT signaling axis. Oncogenesis 28 34642309
2015 TRPC1 regulates fMLP-stimulated migration and chemotaxis of neutrophil granulocytes. Biochimica et biophysica acta 28 25595528
2015 Molecular determinants of TRPC1 regulation within ER-PM junctions. Cell calcium 28 25922260
2008 Evidence that TRPC1 is involved in hippocampal glutamate-induced cell death. Neuroscience letters 28 18822346
2019 Loss of Ca2+ entry via Orai-TRPC1 induces ER stress, initiating immune activation in macrophages. Journal of cell science 27 31722977
2004 Biogenesis and topology of the transient receptor potential Ca2+ channel TRPC1. The Journal of biological chemistry 27 14707123
2022 TRPV4 and TRPC1 channels mediate the response to tensile strain in mouse Müller cells. Cell calcium 26 35398674
2015 Silencing of TRPC1 regulates store-operated calcium entry and proliferation in Huh7 hepatocellular carcinoma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 25960236
2015 Store depletion induces Gαq-mediated PLCβ1 activity to stimulate TRPC1 channels in vascular smooth muscle cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 26467792
2014 Caveolin-1 enhances rapid mucosal restitution by activating TRPC1-mediated Ca2+ signaling. Physiological reports 26 25367694
2011 TRPC1, STIM1, and ORAI influence signal-regulated intracellular and endoplasmic reticulum calcium dynamics in human myometrial cells. Biology of reproduction 26 21565997
2020 TRPC1 participates in the HSV-1 infection process by facilitating viral entry. Science advances 25 32206724
2020 TRPC1 exacerbate metastasis in gastric cancer via ciRS-7/miR-135a-5p/TRPC1 axis. Biochemical and biophysical research communications 25 32560824
2016 SARAF modulates TRPC1, but not TRPC6, channel function in a STIM1-independent manner. The Biochemical journal 25 27506849
2013 TRPC1 protects dopaminergic SH-SY5Y cells from MPP+, salsolinol, and N-methyl-(R)-salsolinol-induced cytotoxicity. Acta biochimica et biophysica Sinica 25 24252728
2006 Regulatory role of neuron-restrictive silencing factor in expression of TRPC1. Biochemical and biophysical research communications 25 17084381
2020 TRPC1/4/5 channels contribute to morphine-induced analgesic tolerance and hyperalgesia by enhancing spinal synaptic potentiation and structural plasticity. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 32359120
2008 Induced TRPC1 expression increases protein phosphatase 2A sensitizing intestinal epithelial cells to apoptosis through inhibition of NF-kappaB activation. American journal of physiology. Cell physiology 24 18322138
2014 Adaptive responses of TRPC1 and TRPC3 during skeletal muscle atrophy and regrowth. Muscle & nerve 23 23852583
2013 Calcium supplementation increases circulating cholesterol by reducing its catabolism via GPER and TRPC1-dependent pathway in estrogen deficient women. International journal of cardiology 23 23602294
2022 TRPC1 contributes to endotoxemia-induced myocardial dysfunction via mediating myocardial apoptosis and autophagy. Pharmacological research 22 35598715
2013 Crucial role of TRPC1 and TRPC4 in cystitis-induced neuronal sprouting and bladder overactivity. PloS one 22 23922735