The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TRPC3  -  transient receptor potential cation...

Homo sapiens

Synonyms: Short transient receptor potential channel 3, TRP-3, TRP3, Transient receptor protein 3, TrpC3, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TRPC3


High impact information on TRPC3

  • TRP-3 is initially localized in intracellular vesicles, and then translocates to the plasma membrane during sperm activation [6].
  • Expression in COS cells of two full-length cDNAs encoding human trp homologs, Htrp1 and Htrp3, increased CCE [7].
  • Although hTRPC3, the closest structural relative of hTRPC6, is activated in the same way, TRPCs 1, 4 and 5 and the vanilloid receptor subtype 1 are unresponsive to the lipid mediator [8].
  • Importantly, carbachol, not thapsigargin, increased surface expression of TRPC3 that was attenuated by TeNT and not by BAPTA [2].
  • Further, endogenous and exogenously expressed TRPC3 colocalized and coimmunoprecipitated with SNARE proteins in neuronal and epithelial cells [2].

Biological context of TRPC3


Anatomical context of TRPC3

  • Immunofluorescence microscopy demonstrated localization of TRPC1, TRPC3, and TRPC4 to the PMN cell membrane and their internalization after cytoskeletal reorganization by calyculin A (CalyA) [12].
  • Using the T3-65 clonal HEK293 cell line stably expressing TRPC3 channels, TRPC3-mediated Sr2+ entry activated by muscarinic receptors was also blocked by BTP2 with an IC50 of <0.3 microM [9].
  • Our data provide the initial step toward understanding the molecular nature of endogenous Ca2+ channels participating in T-cell activation and put forward TRPC3 as a new target for modulating the immune response [13].
  • Endogenously and exogenously expressed TRPC3 was localized apically in polarized Madin-Darby canine kidney cells (MDCK) and salivary gland epithelial cells [14].
  • Most importantly, (i) TRPC3 was detected in the apical region of rat submandibular gland ducts, whereas TRPC6 was present in apical as well as basolateral regions of ducts and acini; and (ii) OAG stimulated Ca2+ influx into dispersed ductal cells [14].

Associations of TRPC3 with chemical compounds

  • What is not known is the step at which src acts on TRPC3 and whether the role for tyrosine kinases in ROCE or SOCE is a general phenomenon [15].
  • 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) [16].
  • Whereas whole-cell carbachol-induced TRPC3 current was blocked by 3 microM BTP2, single TRPC3 channel recordings revealed persistent short openings suggesting BTP2 reduces the open probability of the channel rather than its pore properties [9].
  • 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 [17].
  • The distributions of TRPC3 and TRPC6 between soluble and membrane fractions were not affected by methyl-beta-cyclodextrin treatment [18].

Physical interactions of TRPC3

  • Conversely, TRPC1 co-immunoprecipitated with TRPC3 [19].
  • Glutathione S-transferase pull-down experiments revealed that NCX1 interacts with the cytosolic C terminus of TRPC3 [20].
  • Conformational coupling with the inositol 1,4,5-trisphosphate (IP3) receptor has been suggested as a possible mechanism of activation of TRPC3 channels and a region in the C terminus of TRPC3 has been shown to interact with the IP3 receptor as well as calmodulin (calmodulin/IP3 receptor-binding (CIRB) region) [21].

Enzymatic interactions of TRPC3

  • The C-terminal half of the PLC-gamma split PH domain has been implicated to interact directly with the TRPC3 calcium channel, thereby providing a direct coupling mechanism between PLC-gamma and agonist-induced calcium entry [22].

Co-localisations of TRPC3

  • TRPC3 and -C6 colocalized with aquaporin-2, but not with the Na(+)/Ca(2+) exchanger or peanut lectin [23].

Regulatory relationships of TRPC3

  • TRPC5 channels transiently expressed in HEK293 cells were blocked by BTP2 in the same range as TRPC3 [9].
  • Normal human PASMC expressed multiple canonical TRP (TRPC) isoforms; TRPC6 was highly expressed and TRPC3 was minimally expressed [3].
  • VEGF is also able to activate heterologously expressed TRPC3/6 channels through VEGFR2 [24].
  • 4) Expression of dominant-negative TRPC4 proteins suppressed TRPC3-related channel activity in the HEK293 expression system and in native endothelial cells [25].
  • Based on these data, we conclude that expression of TRPC3 is tightly regulated during muscle cell differentiation and propose that functional interaction between TRPC3 and RyR1 may regulate the gain of SR Ca(2+) release independent of SR Ca(2+) load [26].
  • Substitution of Tyr(226) alone with phenylalanine significantly reduced the Epo-stimulated increase in [Ca(2+)](i) but not the association of PLCgamma with TRPC3 [27].

Other interactions of TRPC3

  • Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol [8].
  • We show that PKD2 can directly associate with TRPC1 but not TRPC3 in transfected cells and in vitro [28].
  • However, mutual swap of VP and IP in TRPC3 and TRPC5 did not alter the association or the selectivity of the channels for their respective immunophilin binding partner [29].
  • Regulation of Ca2+ entry is a key process for lymphocyte activation, and TRP channels may both increase Ca2+ influx (such as TRPC3) or decrease Ca2+ influx through membrane depolarization (such as TRPM4) [30].
  • NCX1 immunoreactivity was detectable in HEK293 as well as in TRPC3-overexpressing HEK293 cells, and reduction of extracellular Na(+) after Na(+) loading with monensin resulted in significant rises in intracellular free Ca(2+) (Ca(2+)(i)) of HEK293 cells [20].
  • Epo-R and phospholipase Cgamma associated with TRPC3, and these interactions were significantly reduced with TRPC6 and TRPC3-C6C chimeras [31].

Analytical, diagnostic and therapeutic context of TRPC3


  1. Role of transient receptor potential C3 in TNF-alpha-enhanced calcium influx in human airway myocytes. White, T.A., Xue, A., Chini, E.N., Thompson, M., Sieck, G.C., Wylam, M.E. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  2. VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to agonist-stimulated Ca2+ influx. Singh, B.B., Lockwich, T.P., Bandyopadhyay, B.C., Liu, X., Bollimuntha, S., Brazer, S.C., Combs, C., Das, S., Leenders, A.G., Sheng, Z.H., Knepper, M.A., Ambudkar, S.V., Ambudkar, I.S. Mol. Cell (2004) [Pubmed]
  3. Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Yu, Y., Fantozzi, I., Remillard, C.V., Landsberg, J.W., Kunichika, N., Platoshyn, O., Tigno, D.D., Thistlethwaite, P.A., Rubin, L.J., Yuan, J.X. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy. Onohara, N., Nishida, M., Inoue, R., Kobayashi, H., Sumimoto, H., Sato, Y., Mori, Y., Nagao, T., Kurose, H. EMBO J. (2006) [Pubmed]
  5. 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]
  6. A C. elegans sperm TRP protein required for sperm-egg interactions during fertilization. Xu, X.Z., Sternberg, P.W. Cell (2003) [Pubmed]
  7. 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]
  8. 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]
  9. A functional link between store-operated and TRPC channels revealed by the 3,5-bis(trifluoromethyl)pyrazole derivative, BTP2. He, L.P., Hewavitharana, T., Soboloff, J., Spassova, M.A., Gill, D.L. J. Biol. Chem. (2005) [Pubmed]
  10. Store-operated Ca2+ entry in first trimester and term human placenta. Clarson, L.H., Roberts, V.H., Hamark, B., Elliott, A.C., Powell, T. J. Physiol. (Lond.) (2003) [Pubmed]
  11. Regulation of canonical transient receptor potential isoform 3 (TRPC3) channel by protein kinase G. Kwan, H.Y., Huang, Y., Yao, X. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  12. Cytoskeletal reorganization internalizes multiple transient receptor potential channels and blocks calcium entry into human neutrophils. Itagaki, K., Kannan, K.B., Singh, B.B., Hauser, C.J. J. Immunol. (2004) [Pubmed]
  13. TRPC3 mediates T-cell receptor-dependent calcium entry in human T-lymphocytes. Philipp, S., Strauss, B., Hirnet, D., Wissenbach, U., Mery, L., Flockerzi, V., Hoth, M. J. Biol. Chem. (2003) [Pubmed]
  14. Apical localization of a functional TRPC3/TRPC6-Ca2+-signaling complex in polarized epithelial cells. Role in apical Ca2+ influx. Bandyopadhyay, B.C., Swaim, W.D., Liu, X., Redman, R.S., Patterson, R.L., Ambudkar, I.S. J. Biol. Chem. (2005) [Pubmed]
  15. Role of Src in C3 transient receptor potential channel function and evidence for a heterogeneous makeup of receptor- and store-operated Ca2+ entry channels. Kawasaki, B.T., Liao, Y., Birnbaumer, L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  16. 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]
  17. 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]
  18. Transient receptor potential protein subunit assembly and membrane distribution in human platelets. Brownlow, S.L., Sage, S.O. Thromb. Haemost. (2005) [Pubmed]
  19. 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]
  20. Ca(2+) signaling by TRPC3 involves Na(+) entry and local coupling to the Na(+)/Ca(2+) exchanger. Rosker, C., Graziani, A., Lukas, M., Eder, P., Zhu, M.X., Romanin, C., Groschner, K. J. Biol. Chem. (2004) [Pubmed]
  21. A calmodulin/inositol 1,4,5-trisphosphate (IP3) receptor-binding region targets TRPC3 to the plasma membrane in a calmodulin/IP3 receptor-independent process. Wedel, B.J., Vazquez, G., McKay, R.R., St J Bird, G., Putney, J.W. J. Biol. Chem. (2003) [Pubmed]
  22. Structural Characterization of the Split Pleckstrin Homology Domain in Phospholipase C-{gamma}1 and Its Interaction with TRPC3. Wen, W., Yan, J., Zhang, M. J. Biol. Chem. (2006) [Pubmed]
  23. 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]
  24. VEGF activates receptor-operated cation channels in human microvascular endothelial cells. Cheng, H.W., James, A.F., Foster, R.R., Hancox, J.C., Bates, D.O. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  25. TRPC3 and TRPC4 Associate to Form a Redox-sensitive Cation Channel: EVIDENCE FOR EXPRESSION OF NATIVE TRPC3-TRPC4 HETEROMERIC CHANNELS IN ENDOTHELIAL CELLS. Poteser, M., Graziani, A., Rosker, C., Eder, P., Derler, I., Kahr, H., Zhu, M.X., Romanin, C., Groschner, K. J. Biol. Chem. (2006) [Pubmed]
  26. Functional coupling between TRPC3 and RyR1 regulates the expressions of key triadic proteins. Lee, E.H., Cherednichenko, G., Pessah, I.N., Allen, P.D. J. Biol. Chem. (2006) [Pubmed]
  27. TRPC3 is the erythropoietin-regulated calcium channel in human erythroid cells. Tong, Q., Hirschler-Laszkiewicz, I., Zhang, W., Conrad, K., Neagley, D.W., Barber, D.L., Cheung, J.Y., Miller, B.A. J. Biol. Chem. (2008) [Pubmed]
  28. 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]
  29. Association of immunophilins with mammalian TRPC channels. Sinkins, W.G., Goel, M., Estacion, M., Schilling, W.P. J. Biol. Chem. (2004) [Pubmed]
  30. TRP channels in lymphocytes. Schwarz, E.C., Wolfs, M.J., Tonner, S., Wenning, A.S., Quintana, A., Griesemer, D., Hoth, M. Handbook of experimental pharmacology (2007) [Pubmed]
  31. TRPC3 activation by erythropoietin is modulated by TRPC6. Hirschler-Laszkiewicz, I., Tong, Q., Conrad, K., Zhang, W., Flint, W.W., Barber, A.J., Barber, D.L., Cheung, J.Y., Miller, B.A. J. Biol. Chem. (2009) [Pubmed]
  32. 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]
  33. Functional significance of human trp1 and trp3 in store-operated Ca(2+) entry in HEK-293 cells. Wu, X., Babnigg, G., Villereal, M.L. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  34. Negative regulation of TRPC3 channels by protein kinase C-mediated phosphorylation of serine 712. Trebak, M., Hempel, N., Wedel, B.J., Smyth, J.T., Bird, G.S., Putney, J.W. Mol. Pharmacol. (2005) [Pubmed]
WikiGenes - Universities