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Gene Review

TRPC1  -  transient receptor potential cation...

Homo sapiens

Synonyms: HTRP-1, Short transient receptor potential channel 1, TRP-1, TRP1, Transient receptor protein 1, ...
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Disease relevance of TRPC1


High impact information on TRPC1

  • Expression in COS cells of two full-length cDNAs encoding human trp homologs, Htrp1 and Htrp3, increased CCE [6].
  • Drosophila transient receptor potential (TRP) proteins and some mammalian homologues (TRPC proteins) are thought to mediate capacitative Ca2+ entry [7].
  • Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1 [8].
  • Notably, the cytosolic carboxyl terminus of STIM1 is sufficient to activate SOC, I(crac) and TRPC1 channels even when native STIM1 is depleted by small interfering RNA [9].
  • Deletion of either region in the constitutively active STIM1(D76A) yields dominant-negative mutants that block native SOC channels, expressed TRPC1 in HEK293 cells and I(crac) in Jurkat cells [9].

Chemical compound and disease context of TRPC1


Biological context of TRPC1


Anatomical context of TRPC1


Associations of TRPC1 with chemical compounds

  • TRPC1/TRPC5 heteromers were activated by G(q)-coupled receptors but not by depletion of intracellular Ca(2+) stores [19].
  • The suppression of either TRPC3 or TRPC7, but not TRPC1, induced a high Ba(2+) leak flux that was inhibited by 2-APB and SKF96365, suggesting that the influx is via leaky store-operated channels [20].
  • These results suggest that TRPC1, -C3, and -C6 may play a functional role in PLC-dependent signaling in specific regions of the nephron [16].
  • Thus lowering the levels of cellular calcium with the chelators EGTA and BAPTA AM results in a downregulation of TRPC1-TRPC4 gene and protein expression [21].
  • It encodes a putative variant of the C3-type TRPC (transient receptor potential channel) that differs from the previously cloned murine TRPC3 cDNA in that it has a 5' extension stemming from inclusion of an additional exon (exon 0) [22].
  • Overexpression of TRPC1 or SERCA2-siRNA in HaCaT cells demonstrated resistance to thapsigargin-induced apoptosis [23].
  • TRPC isolation from protein complexes using ProCISA revealed that hTRPC1, 4 and 5 were not tyrosine phosphorylated at rest or after Thr stimulation [24].
  • Electrotransjection of cells with anti-Orai1 antibody, directed toward the C-terminal region that mediates the interaction with STIM1, and stabilization of an actin cortical barrier with jasplakinolide prevented the interaction between STIM1 and hTRPC1 [25].

Physical interactions of TRPC1

  • Conversely, TRPC1 co-immunoprecipitated with TRPC3 [26].
  • Using a GST pull-down and co-immunoprecipitation assay, we showed that MxA interacted with TRPC1, -3, -4, -5, -6, and -7 [27].
  • The purpose of the present study was to determine if mammalian FKBP12 or FKBP52 interact with TRPC channel proteins [28].
  • Full-length Cav1 bound to both the N and C termini of TRPC1 [29].
  • We found that the synaptosome-associated protein (SNAP-25) and the vesicle-associated membrane proteins (VAMP) coimmunoprecipitate with hTRPC1 in platelets [30].

Regulatory relationships of TRPC1


Other interactions of TRPC1

  • The C-terminal domain is sufficient but not necessary for the PKD2-TRPC1 association [33].
  • However, distinct residues within this region mediate specific interactions with TRPC1 or PKD1 [33].
  • Furthermore, coimmunoprecipitation experiments and immunofluorescent double staining displayed that TRPC1 had physical interaction with TRPC4 and 6, while no interactions were detected among other isoforms of TRPCs [34].
  • After dilatation, TRPC1 and TRPC6 mRNA were progressively increased compared with undilated control segments [14].
  • This study investigated gestational regulation of transient receptor potential canonical (TrpC) proteins, putative calcium entry channels in human myometrium, and the potential modulation of TrpC expression by IL-1 beta, a cytokine implicated in labor [35].

Analytical, diagnostic and therapeutic context of TRPC1


  1. Capacitative Ca2+ entries and mRNA expression for TRPC1 and TRPC5 channels in human epidermoid carcinoma A431 cells. Yoshida, J., Ishibashi, T., Imaizumi, N., Takegami, T., Nishio, M. Eur. J. Pharmacol. (2005) [Pubmed]
  2. Transient receptor potential channels in cardiovascular function and disease. Inoue, R., Jensen, L.J., Shi, J., Morita, H., Nishida, M., Honda, A., Ito, Y. Circ. Res. (2006) [Pubmed]
  3. TRPC1-mediated inhibition of 1-methyl-4-phenylpyridinium ion neurotoxicity in human SH-SY5Y neuroblastoma cells. Bollimuntha, S., Singh, B.B., Shavali, S., Sharma, S.K., Ebadi, M. J. Biol. Chem. (2005) [Pubmed]
  4. Receptor-coupled, DAG-gated Ca2+-permeable cationic channels in LNCaP human prostate cancer epithelial cells. Sydorenko, V., Shuba, Y., Thebault, S., Roudbaraki, M., Lepage, G., Prevarskaya, N., Skryma, R. J. Physiol. (Lond.) (2003) [Pubmed]
  5. Pharmacological and electrophysiological characterization of store-operated currents and capacitative Ca2+ entry in vascular smooth muscle cells. Brueggemann, L.I., Markun, D.R., Henderson, K.K., Cribbs, L.L., Byron, K.L. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  6. trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Zhu, X., Jiang, M., Peyton, M., Boulay, G., Hurst, R., Stefani, E., Birnbaumer, L. Cell (1996) [Pubmed]
  7. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Hofmann, T., Obukhov, A.G., Schaefer, M., Harteneck, C., Gudermann, T., Schultz, G. Nature (1999) [Pubmed]
  8. Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1. Singh, B.B., Liu, X., Tang, J., Zhu, M.X., Ambudkar, I.S. Mol. Cell (2002) [Pubmed]
  9. STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels. Huang, G.N., Zeng, W., Kim, J.Y., Yuan, J.P., Han, L., Muallem, S., Worley, P.F. Nat. Cell Biol. (2006) [Pubmed]
  10. TRPC1 protects human SH-SY5Y cells against salsolinol-induced cytotoxicity by inhibiting apoptosis. Bollimuntha, S., Ebadi, M., Singh, B.B. Brain Res. (2006) [Pubmed]
  11. Tumor necrosis factor-alpha induces nuclear factor-kappaB-dependent TRPC1 expression in endothelial cells. Paria, B.C., Malik, A.B., Kwiatek, A.M., Rahman, A., May, M.J., Ghosh, S., Tiruppathi, C. J. Biol. Chem. (2003) [Pubmed]
  12. Phospholipase cgamma1 is required for activation of store-operated channels in human keratinocytes. Tu, C.L., Chang, W., Bikle, D.D. J. Invest. Dermatol. (2005) [Pubmed]
  13. Transient receptor potential protein subunit assembly and membrane distribution in human platelets. Brownlow, S.L., Sage, S.O. Thromb. Haemost. (2005) [Pubmed]
  14. Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca2+ entry. Bergdahl, A., Gomez, M.F., Wihlborg, A.K., Erlinge, D., Eyjolfson, A., Xu, S.Z., Beech, D.J., Dreja, K., Hellstrand, P. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  15. Expression of transient receptor potential C6 and related transient receptor potential family members in human airway smooth muscle and lung tissue. Corteling, R.L., Li, S., Giddings, J., Westwick, J., Poll, C., Hall, I.P. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  16. Identification and localization of TRPC channels in the rat kidney. Goel, M., Sinkins, W.G., Zuo, C.D., Estacion, M., Schilling, W.P. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  17. Expression of human TRPC genes in the megakaryocytic cell lines MEG01, DAMI and HEL. Berg, L.P., Shamsher, M.K., El-Daher, S.S., Kakkar, V.V., Authi, K.S. FEBS Lett. (1997) [Pubmed]
  18. TRPC1 store-operated cationic channel subunit. Beech, D.J., Xu, S.Z., McHugh, D., Flemming, R. Cell Calcium (2003) [Pubmed]
  19. TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Strübing, C., Krapivinsky, G., Krapivinsky, L., Clapham, D.E. Neuron (2001) [Pubmed]
  20. Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells. Zagranichnaya, T.K., Wu, X., Villereal, M.L. J. Biol. Chem. (2005) [Pubmed]
  21. Calcium controls smooth muscle TRPC gene transcription via the CaMK/calcineurin-dependent pathways. Morales, S., Diez, A., Puyet, A., Camello, P.J., Camello-Almaraz, C., Bautista, J.M., Pozo, M.J. Am. J. Physiol., Cell Physiol. (2007) [Pubmed]
  22. Molecular cloning of TRPC3a, an N-terminally extended, store-operated variant of the human C3 transient receptor potential channel. Yildirim, E., Kawasaki, B.T., Birnbaumer, L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  23. Up-regulation of transient receptor potential canonical 1 (TRPC1) following sarco(endo)plasmic reticulum Ca2+ ATPase 2 gene silencing promotes cell survival: a potential role for TRPC1 in Darier's disease. Pani, B., Cornatzer, E., Cornatzer, W., Shin, D.M., Pittelkow, M.R., Hovnanian, A., Ambudkar, I.S., Singh, B.B. Mol. Biol. Cell (2006) [Pubmed]
  24. hTRPC1-associated alpha-actinin, and not hTRPC1 itself, is tyrosine phosphorylated during human platelet activation. Redondo, P.C., Harper, A.G., Harper, M.T., Brownlow, S.L., Rosado, J.A., Sage, S.O. J. Thromb. Haemost. (2007) [Pubmed]
  25. Orai1 mediates the interaction between STIM1 and hTRPC1 and regulates the mode of activation of hTRPC1-forming Ca2+ channels. Jardin, I., Lopez, J.J., Salido, G.M., Rosado, J.A. J. Biol. Chem. (2008) [Pubmed]
  26. Molecular analysis of a store-operated and 2-acetyl-sn-glycerol-sensitive non-selective cation channel. Heteromeric assembly of TRPC1-TRPC3. Liu, X., Bandyopadhyay, B.C., Singh, B.B., Groschner, K., Ambudkar, I.S. J. Biol. Chem. (2005) [Pubmed]
  27. MxA, a member of the dynamin superfamily, interacts with the ankyrin-like repeat domain of TRPC. Lussier, M.P., Cayouette, S., Lepage, P.K., Bernier, C.L., Francoeur, N., St-Hilaire, M., Pinard, M., Boulay, G. J. Biol. Chem. (2005) [Pubmed]
  28. Association of immunophilins with mammalian TRPC channels. Sinkins, W.G., Goel, M., Estacion, M., Schilling, W.P. J. Biol. Chem. (2004) [Pubmed]
  29. Caveolin-1 contributes to assembly of store-operated Ca2+ influx channels by regulating plasma membrane localization of TRPC1. Brazer, S.C., Singh, B.B., Liu, X., Swaim, W., Ambudkar, I.S. J. Biol. Chem. (2003) [Pubmed]
  30. A role for SNAP-25 but not VAMPs in store-mediated Ca2+ entry in human platelets. Redondo, P.C., Harper, A.G., Salido, G.M., Pariente, J.A., Sage, S.O., Rosado, J.A. J. Physiol. (Lond.) (2004) [Pubmed]
  31. Angiopoietin-1 opposes VEGF-induced increase in endothelial permeability by inhibiting TRPC1-dependent Ca2 influx. Jho, D., Mehta, D., Ahmmed, G., Gao, X.P., Tiruppathi, C., Broman, M., Malik, A.B. Circ. Res. (2005) [Pubmed]
  32. A sphingosine-1-phosphate-activated calcium channel controlling vascular smooth muscle cell motility. Xu, S.Z., Muraki, K., Zeng, F., Li, J., Sukumar, P., Shah, S., Dedman, A.M., Flemming, P.K., McHugh, D., Naylor, J., Cheong, A., Bateson, A.N., Munsch, C.M., Porter, K.E., Beech, D.J. Circ. Res. (2006) [Pubmed]
  33. Specific association of the gene product of PKD2 with the TRPC1 channel. Tsiokas, L., Arnould, T., Zhu, C., Kim, E., Walz, G., Sukhatme, V.P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  34. Expression of canonical transient receptor potential (TRPC) proteins in human glomerular mesangial cells. Sours, S., Du, J., Chu, S., Ding, M., Zhou, X.J., Ma, R. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  35. Physiological induction of transient receptor potential canonical proteins, calcium entry channels, in human myometrium: influence of pregnancy, labor, and interleukin-1 beta. Dalrymple, A., Slater, D.M., Poston, L., Tribe, R.M. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  36. Enhanced capacitative calcium entry and TRPC channel gene expression in human LES smooth muscle. Wang, J., Laurier, L.G., Sims, S.M., Preiksaitis, H.G. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
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