Skip to main content

Advertisement

SpringerLink
Log in

TRPC1: store-operated channel and more

  • Invited Review
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Transient receptor potential canonical 1 (TRPC1) is a transmembrane protein expressed in a range of vertebrate cells including smooth muscle, endothelium, neurones and salivary gland cells. It functions as an element of a mixed cationic Ca2+-permeable channel, probably commonly as part of a heterotetrameric assembly involving other related proteins such as TRPC5. Wide-ranging biological roles of TRPC1 are suggested, including regulation of smooth muscle and stem cell proliferation, endothelin-evoked arterial contraction, salivary gland secretion, endothelial permeability, glutamatergic neurotransmission, growth cone turning, neuroprotection, neuronal differentiation, lipid raft integrity and the nuclear factor of activated T-cell transcription factor. The mechanisms by which TRPC1 serves these functions are starting to emerge. At one level, it is apparent that TRPC1 is subcellularly compartmentalised, at least in part in cholesterol-rich caveolae closely associated with sub-plasmalemmal endoplasmic reticulum. At another level, TRPC1 is embedded in a protein complex that can include inositol trisphosphate receptor, homer, calmodulin, caveolin-1, FKBP25, I-mfa, MxA, GluR1α, bFGFR-1, Gq/11 protein, phospholipase C-β/γ, protein kinase C-α and RhoA. It is also apparent that TRPC1 responds to general stimuli—not only depletion of intracellular Ca2+ stores, but also receptor activation, and membrane stretch. We are at the early stages of understanding of how these various signals and components integrate to form a functional channel, and this article provides a brief overview of current progress.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ahmmed GU, Mehta D, Vogel S, Holinstat M, Paria BC, Tiruppathi C, Malik AB (2004) Protein kinase Calpha phosphorylates the TRPC1 channel and regulates store-operated Ca2+ entry in endothelial cells. J Biol Chem 279:20941–20949

    CAS  PubMed  Google Scholar 

  2. Albert AP, Large WA (2002) Activation of store-operated channels by noradrenaline via protein kinase C in rabbit portal vein myocytes. J Physiol 544:113–125

    Article  CAS  PubMed  Google Scholar 

  3. Antoniotti S, Lovisolo D, Fiorio Pla A, Munaron L (2002) Expression and functional role of bTRPC1 channels in native endothelial cells. FEBS Lett 510:189–195

    CAS  PubMed  Google Scholar 

  4. Beech DJ, Xu SZ, McHugh D, Flemming R (2003) TRPC1 store-operated cationic channel subunit. Cell Calcium 33:433–440

    Article  CAS  PubMed  Google Scholar 

  5. Bergdahl A, Gomez MF, Dreja K, Xu SZ, Adner M, Beech DJ, Broman J, Hellstrand P, Sward K (2003) Cholesterol depletion impairs vascular reactivity to endothelin-1 by reducing store-operated Ca2+ entry dependent on TRPC1. Circ Res 93:839–847

    Article  CAS  PubMed  Google Scholar 

  6. Bergdahl A, Gomez MF, Wihlborg AK, Erlinge D, Eyjolfson A, Xu SZ, Beech DJ, Dreja K, Hellstrand P (2005) Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca2+ entry. Am J Physiol 288:C872–880

    Article  CAS  Google Scholar 

  7. Berthier A, Lemaire-Ewing S, Prunet C, Monier S, Athias A, Bessede G, Pais de Barros JP, Laubriet A, Gambert P, Lizard G, Neel D (2004) Involvement of a calcium-dependent dephosphorylation of BAD associated with the localization of Trpc-1 within lipid rafts in 7-ketocholesterol-induced THP-1 cell apoptosis. Cell Death Differ 11:897–905

    Article  CAS  PubMed  Google Scholar 

  8. Bollimuntha S, Singh BB, Shavali S, Sharma SK, Ebadi M (2005) TRPC1-mediated inhibition of 1-methyl-4-phenylpyridinium ion neurotoxicity in human SH-SY5Y neuroblastoma cells. J Biol Chem 280:2132–2140

    Article  CAS  PubMed  Google Scholar 

  9. Brazer SC, Singh BB, Liu X, Swaim W, Ambudkar IS (2003) Caveolin-1 contributes to assembly of store-operated Ca2+ influx channels by regulating plasma membrane localization of TRPC1. J Biol Chem 278:27208–27215

    Article  CAS  PubMed  Google Scholar 

  10. Brereton HM, Chen J, Rychkov G, Harland ML, Barritt GJ (2001) Maitotoxin activates an endogenous non-selective cation channel and is an effective initiator of the activation of the heterologously expressed hTRPC-1 (transient receptor potential) non-selective cation channel in H4-IIE liver cells. Biochim Biophys Acta 1540:107–126

    Article  CAS  PubMed  Google Scholar 

  11. Brough GH, Wu S, Cioffi D, Moore TM, Li M, Dean N, Stevens T (2001) Contribution of endogenously expressed Trp1 to a Ca2+-selective, store-operated Ca2+ entry pathway. FASEB J 15:1727–1738

    CAS  PubMed  Google Scholar 

  12. Brownlow SL, Harper AG, Harper MT, Sage SO (2004) A role for hTRPC1 and lipid raft domains in store-mediated calcium entry in human platelets. Cell Calcium 35:107–113

    Article  CAS  PubMed  Google Scholar 

  13. Chen J, Barritt GJ (2003) Evidence that TRPC1 (transient receptor potential canonical 1) forms a Ca2+-permeable channel linked to the regulation of cell volume in liver cells obtained using small interfering RNA targeted against TRPC1. Biochem J 373:327–336

    Article  CAS  PubMed  Google Scholar 

  14. Chuang HH, Neuhausser WM, Julius D (2004) The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel. Neuron 43:859–869

    CAS  PubMed  Google Scholar 

  15. Dalrymple A, Slater DM, Beech D, Poston L, Tribe RM (2002) Molecular identification and localization of Trp homologues, putative calcium channels, in pregnant human uterus. Mol Hum Reprod 8:946–951

    Article  CAS  PubMed  Google Scholar 

  16. Delmas P, Wanaverbecq N, Abogadie FC, Mistry M, Brown DA (2002) Signaling microdomains define the specificity of receptor-mediated InsP3 pathways in neurons. Neuron 34:209–220

    Article  CAS  PubMed  Google Scholar 

  17. Dohke Y, Oh YS, Ambudkar IS, Turner RJ (2004) Biogenesis and topology of the transient receptor potential Ca2+ channel TRPC1. J Biol Chem 279:12242–12248

    Article  CAS  PubMed  Google Scholar 

  18. Engelke M, Friedrich O, Budde P, Schafer C, Niemann U, Zitt C, Jungling E, Rocks O, Luckhoff A, Frey J (2002) Structural domains required for channel function of the mouse transient receptor potential protein homologue TRP1beta. FEBS Lett 523:193–199

    Article  CAS  PubMed  Google Scholar 

  19. Flemming R, Cheong A, Dedman AM, Beech DJ (2002) Discrete store-operated calcium influx into an intracellular compartment in rabbit arteriolar smooth muscle. J Physiol 543:455–464

    Article  CAS  PubMed  Google Scholar 

  20. Goel M, Sinkins WG, Schilling WP (2002) Selective association of TRPC channel subunits in rat brain synaptosomes. J Biol Chem 277:48303–48310

    Article  CAS  PubMed  Google Scholar 

  21. Golovina VA (2005) Visualization of localized store-operated calcium entry in mouse astrocytes. Close proximity to the endoplasmic reticulum. J Physiol 564:737–749

    Article  PubMed  Google Scholar 

  22. Greka A, Navarro B, Oancea E, Duggan A, Clapham DE (2003) TRPC5 is a regulator of hippocampal neurite length and growth cone morphology. Nat Neurosci 6:837–845

    Article  CAS  PubMed  Google Scholar 

  23. Hofmann T, Schaefer M, Schultz G, Gudermann T (2002) Subunit composition of mammalian transient receptor potential channels in living cells. Proc Natl Acad Sci USA 99:7461–7466

    Article  CAS  PubMed  Google Scholar 

  24. Jaconi M, Pyle J, Bortolon R, Ou J, Clapham D (1997) Calcium release and influx colocalize to the endoplasmic reticulum. Curr Biol 7:599–602

    Article  CAS  PubMed  Google Scholar 

  25. Kim SJ, Kim YS, Yuan JP, Petralia RS, Worley PF, Linden DJ (2003) Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1. Nature 426:285–291

    Article  CAS  PubMed  Google Scholar 

  26. Kunichika N, Yu Y, Remillard CV, Platoshyn O, Zhang S, Yuan JX (2004) Overexpression of TRPC1 enhances pulmonary vasoconstriction induced by capacitative Ca2+ entry. Am J Physiol Lung 287, L962–L969

    Article  CAS  Google Scholar 

  27. Kunzelmann-Marche C, Freyssinet JM, Martinez MC (2002) Loss of plasma membrane phospholipid asymmetry requires raft integrity. Role of transient receptor potential channels and ERK pathway. J Biol Chem 277:19876–19881

    Article  CAS  PubMed  Google Scholar 

  28. Larsson KP, Peltonen HM, Bart G, Louhivuori LM, Penttonen A, Antikainen M, Kukkonen JP, Akerman KE (2005) Orexin-A-induced Ca2+ entry: evidence for involvement of trpc channels and protein kinase C regulation. J Biol Chem 280:1771–1781

    Article  CAS  PubMed  Google Scholar 

  29. Lee CH, Poburko D, Kuo KH, Seow CY, van Breemen C (2002) Ca(2+) oscillations, gradients, and homeostasis in vascular smooth muscle. Am J Physiol 282:H1571–H1583

    CAS  Google Scholar 

  30. Lievremont JP, Bird GS, Putney JW Jr (2004) Canonical transient receptor potential TRPC7 can function as both a receptor- and store-operated channel in HEK-293 cells. Am J Physiol 287:C1709–C1716

    Article  CAS  PubMed  Google Scholar 

  31. Lin MJ, Leung GP, Zhang WM, Yang XR, Yip KP, Tse CM, Sham JS (2004) Chronic hypoxia-induced upregulation of store-operated and receptor-operated Ca2+ channels in pulmonary arterial smooth muscle cells: a novel mechanism of hypoxic pulmonary hypertension. Circ Res 95:496–505

    Article  CAS  PubMed  Google Scholar 

  32. Lintschinger B, Balzer-Geldsetzer M, Baskaran T, Graier WF, Romanin C, Zhu MX, Groschner K (2000) Coassembly of Trp1 and Trp3 proteins generates diacylglycerol- and Ca2+-sensitive cation channels. J Biol Chem 275:27799–27805

    CAS  PubMed  Google Scholar 

  33. Liu X, Wang W, Singh BB, Lockwich T, Jadlowiec J, O’Connell B, Wellner R, Zhu MX, Ambudkar IS (2000) Trp1, a candidate protein for the store-operated Ca2+ influx mechanism in salivary gland cells. J Biol Chem 275:3403–3411

    Article  CAS  PubMed  Google Scholar 

  34. Liu X, Singh BB, Ambudkar IS (2003) TRPC1 is required for functional store-operated Ca2+ channels. Role of acidic amino acid residues in the S5-S6 region. J Biol Chem 278:11337–11343

    Article  CAS  PubMed  Google Scholar 

  35. Lockwich TP, Liu X, Singh BB, Jadlowiec J, Weiland S, Ambudkar IS (2000) Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains. J Biol Chem 275:11934–11942

    CAS  PubMed  Google Scholar 

  36. Lussier MP, Cayouette S, Lepage PK, Bernier CL, Francoeur N, St-Hilaire M, Pinard M, Boulay G (2005) MxA, a member of the dynamin superfamily interacts with the ankyrin-like repeat domain of TRPC. J Biol Chem 280:19393–19400

    CAS  PubMed  Google Scholar 

  37. Ma R, Rundle D, Jacks J, Koch M, Downs T, Tsiokas L (2003) Inhibitor of myogenic family, a novel suppressor of store-operated currents through an interaction with TRPC1. J Biol Chem 278:52763–52772

    Article  CAS  PubMed  Google Scholar 

  38. Maroto R, Raso A, Wood TG, Kurosky A, Martinac B, Hamill OP (2005) TRPC1 forms the stretch-activated cation channel in vertebrate cells. Nat Cell Biol 7:179–185

    Article  CAS  PubMed  Google Scholar 

  39. McHugh D, Flemming R, Xu SZ, Perraud AL, Beech DJ (2003) Critical intracellular Ca2+ dependence of transient receptor potential melastatin 2 (TRPM2) cation channel activation. J Biol Chem 278:11002–11006

    CAS  PubMed  Google Scholar 

  40. Mehta D, Ahmmed GU, Paria BC, Holinstat M, Voyno-Yasenetskaya T, Tiruppathi C, Minshall RD, Malik AB (2003) RhoA interaction with inositol 1,4,5-trisphosphate receptor and transient receptor potential channel-1 regulates Ca2+ entry. Role in signaling increased endothelial permeability. J Biol Chem 278:33492–33500

    CAS  Google Scholar 

  41. Mori Y, Wakamori M, Miyakawa T, Hermosura M, Hara Y, Nishida M, Hirose K, Mizushima A, Kurosaki M, Mori E, Gotoh K, Okada T, Fleig A, Penner R, Iino M, Kurosaki T (2002) Transient receptor potential 1 regulates capacitative Ca2+ entry and Ca2+ release from endoplasmic reticulum in B lymphocytes. J Exp Med 195:673–681

    Article  CAS  PubMed  Google Scholar 

  42. Paria BC, Vogel SM, Ahmmed GU, Alamgir S, Shroff J, Malik AB, Tiruppathi C (2004) Tumor necrosis factor-alpha-induced TRPC1 expression amplifies store-operated Ca2+ influx and endothelial permeability. Am J Physiol 287:L1303–L1313

    CAS  Google Scholar 

  43. Pla AF, Maric D, Brazer SC, Giacobini P, Liu X, Chang YH, Ambudkar IS, Barker JL (2005) Canonical transient receptor potential 1 plays a role in basic fibroblast growth factor (bFGF)/FGF receptor-1-induced Ca2+ entry and embryonic rat neural stem cell proliferation. J Neurosci 25:2687–2701

    Google Scholar 

  44. Rosado JA, Sage SO (2000) Coupling between inositol 1,4,5-trisphosphate receptors and human transient receptor potential channel 1 when intracellular Ca2+ stores are depleted. Biochem J 350 (Pt 3):631–635

    Article  CAS  PubMed  Google Scholar 

  45. Rosado JA, Brownlow SL, Sage SO (2002) Endogenously expressed Trp1 is involved in store-mediated Ca2+ entry by conformational coupling in human platelets. J Biol Chem 277:42157–42163

    CAS  PubMed  Google Scholar 

  46. Singh BB, Liu X, Tang J, Zhu MX, Ambudkar IS (2002) Calmodulin regulates Ca2+-dependent feedback inhibition of store-operated Ca2+ influx by interaction with a site in the C terminus of TrpC1. Mol Cell 9:739–750

    Article  CAS  PubMed  Google Scholar 

  47. Sinkins WG, Goel M, Estacion M, Schilling WP (2004) Association of immunophilins with mammalian TRPC channels. J Biol Chem 279:34521–34529

    CAS  PubMed  Google Scholar 

  48. Strubing C, Krapivinsky G, Krapivinsky L, Clapham DE (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29:645–655

    Article  PubMed  Google Scholar 

  49. Strubing C, Krapivinsky G, Krapivinsky L, Clapham DE (2003) Formation of novel TRPC channels by complex subunit interactions in embryonic brain. J Biol Chem 278:39014–39019

    Article  PubMed  Google Scholar 

  50. Sweeney M, Yu Y, Platoshyn O, Zhang S, McDaniel SS, Yuan JX (2002) Inhibition of endogenous TRP1 decreases capacitative Ca2+ entry and attenuates pulmonary artery smooth muscle cell proliferation. Am J Physiol 283:L144–L155

    CAS  Google Scholar 

  51. Tang J, Lin Y, Zhang Z, Tikunova S, Birnbaumer L, Zhu MX (2001) Identification of common binding sites for calmodulin and inositol 1,4,5-trisphosphate receptors on the carboxyl termini of trp channels. J Biol Chem 276:21303–21310

    Article  CAS  PubMed  Google Scholar 

  52. Tsiokas L, Arnould T, Zhu C, Kim E, Walz G, Sukhatme VP (1999) Specific association of the gene product of PKD2 with the TRPC1 channel. Proc Natl Acad Sci USA 96:3934–3939

    Article  CAS  PubMed  Google Scholar 

  53. Tu CL, Chang W, Bikle DD (2005) Phospholipase cgamma1 is required for activation of store-operated channels in human keratinocytes. J Invest Dermatol 124:187–197

    Article  CAS  PubMed  Google Scholar 

  54. Vaca L, Sampieri A (2002) Calmodulin modulates the delay period between release of calcium from internal stores and activation of calcium influx via endogenous TRP1 channels. J Biol Chem 277:42178–42187

    Article  CAS  PubMed  Google Scholar 

  55. Vandebrouck C, Martin D, Colson-Van Schoor M, Debaix H, Gailly P (2002) Involvement of TRPC in the abnormal calcium influx observed in dystrophic (mdx) mouse skeletal muscle fibers. J Cell Biol 158:1089–1096

    Article  CAS  PubMed  Google Scholar 

  56. Vannier B, Zhu X, Brown D, Birnbaumer L (1998) The membrane topology of human transient receptor potential 3 as inferred from glycosylation-scanning mutagenesis and epitope immunocytochemistry. J Biol Chem 273:8675–8679

    Article  CAS  PubMed  Google Scholar 

  57. Venkatachalam K, van Rossum DB, Patterson RL, Ma HT, Gill DL (2002) The cellular and molecular basis of store-operated calcium entry. Nat Cell Biol 4:E263–E272

    Article  CAS  PubMed  Google Scholar 

  58. Wang W, O’Connell B, Dykeman R, Sakai T, Delporte C, Swaim W, Zhu X, Birnbaumer L, Ambudkar IS (1999) Cloning of Trp1beta isoform from rat brain: immunodetection and localization of the endogenous Trp1 protein. Am J Physiol 276:C969–C979

    CAS  PubMed  Google Scholar 

  59. Wang GX, Poo MM (2005) Requirement of TRPC channels in netrin-1-induced chemotropic turning of nerve growth cones. Nature 434:898–904

    Google Scholar 

  60. Wes PD, Chevesich J, Jeromin A, Rosenberg C, Stetten G, Montell C (1995) TRPC1, a human homolog of a Drosophila store-operated channel. Proc Natl Acad Sci USA 92:9652–9656

    CAS  PubMed  Google Scholar 

  61. Wu X, Babnigg G, Villereal ML (2000) Functional significance of human trp1 and trp3 in store-operated Ca2+ entry in HEK-293 cells. Am J Physiol 278:C526–C536

    CAS  PubMed  Google Scholar 

  62. Wu X, Zagranichnaya TK, Gurda GT, Eves EM, Villereal ML (2004) A TRPC1/TRPC3-mediated increase in store-operated calcium entry is required for differentiation of H19–7 hippocampal neuronal cells. J Biol Chem 279:43392–43402

    Article  CAS  PubMed  Google Scholar 

  63. Xu SZ, Beech DJ (2001) TrpC1 is a membrane-spanning subunit of store-operated Ca2+ channels in native vascular smooth muscle cells. Circ Res 88:84–87

    CAS  PubMed  Google Scholar 

  64. Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S, Worley PF (2003) Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell 114:777–789

    CAS  PubMed  Google Scholar 

  65. Zeng F, Xu SZ, Jackson PK, McHugh D, Kumar B, Fountain SJ, Beech DJ (2004) Human TRPC5 channel activated by a multiplicity of signals in a single cell. J Physiol 559:739–750

    CAS  PubMed  Google Scholar 

  66. Zhu X, Chu PB, Peyton M, Birnbaumer L (1995) Molecular cloning of a widely expressed human homologue for the Drosophila trp gene. FEBS Lett 373:193–198

    Article  CAS  PubMed  Google Scholar 

  67. Zitt C, Zobel A, Obukhov AG, Harteneck C, Kalkbrenner F, Luckhoff A, Schultz G (1996) Cloning and functional expression of a human Ca2+-permeable cation channel activated by calcium store depletion. Neuron 16:1189–1196

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Wellcome Trust and British Heart Foundation.

Author information

Authors and Affiliations

  1. School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK

    David J Beech

Authors
  1. David J Beech
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David J Beech.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beech, D.J. TRPC1: store-operated channel and more. Pflugers Arch - Eur J Physiol 451, 53–60 (2005). https://doi.org/10.1007/s00424-005-1441-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-005-1441-3

Keywords

Search

Navigation