| 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
|