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Gene Review

TRPC5  -  transient receptor potential cation...

Homo sapiens

Synonyms: PPP1R159, Short transient receptor potential channel 5, TRP-5, TRP5, Transient receptor protein 5, ...
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Disease relevance of TRPC5


Psychiatry related information on TRPC5


High impact information on TRPC5

  • The increase in TRPC5 availability affects neurite extension rates in cultured hippocampal neurons, and may be a general mechanism for initiating Ca(2+) influx and cell morphological changes in response to stimuli [4].
  • Here, we report that growth factor stimulation initiates the rapid translocation of the transient receptor potential ion channel, TRPC5, from vesicles held in reserve just under the plasma membrane [4].
  • TRPC1/TRPC5 heteromers were activated by G(q)-coupled receptors but not by depletion of intracellular Ca(2+) stores [5].
  • LPC activated TRPC5 when applied to excised membrane patches and thus has a relatively direct action on the channel structure, either because of a phospholipid binding site on the channel or because of sensitivity of the channel to perturbation of the bilayer by certain lipids [6].
  • We have revealed that one of the TRPC channels, TRPC5, is strongly activated by common endogenous lysophospholipids including lysophosphatidylcholine (LPC) but, by contrast, not arachidonic acid [6].

Biological context of TRPC5

  • We conclude that the VTTRL motif is not necessary for activation of TRPC5, but may mediate the modulatory effect of EBP50 on TRPC5 activation kinetics [7].
  • 7 Block of TRP channels by 2-APB may be relevant to cell proliferation because 2-APB has a greater inhibitory effect on proliferation in cells overexpressing TRPC5 [8].
  • We conclude that the desensitization of TRPC5 occurs via PKC phosphorylation and suggest that threonine at residue 972 of mouse TRPC5 might be required for its phosphorylation by PKC [9].
  • Differentiated IEC-Cdx2L1 cells induced by forced expression of the Cdx2 gene highly expressed endogenous TRPC1 and TRPC5 and exhibited increased CCE and cell migration [10].
  • We find that intracellular Mg2+ blocks the outward current through TRPC5 with an IC50 of 457 microM [11].

Anatomical context of TRPC5


Associations of TRPC5 with chemical compounds

  • Whole cell currents through TRPC5 were reversibly potentiated by micromolar concentrations of La(3+) or Gd(3+), whereas millimolar concentrations were inhibitory [17].
  • Mutant NCS-1 does not inhibit surface-expression of TRPC5 but generally suppresses channel activity, irrespective of whether it is evoked by carbachol, store depletion, lanthanides or elevated intracellular calcium [18].
  • In addition, and in the absence of receptor stimulation, extracellular gadolinium (0.1 mm) activated TRPC5, an effect that was mimicked by 5-20 mm extracellular Ca2+ with intracellular Ca2+ buffered [19].
  • When TRPC5 current was activated by intracellular GTPgammaS, PKC inhibitors prevented TRPC5 desensitization and the mutation of TRPC5 T972 to alanine slowed the desensitization process dramatically [9].
  • This paper provides a brief and focused review of our latest findings that show that TRPC5 is a sensor of important signalling phospholipids, including lysophosphatidylcholine and sphingosine 1-phosphate, acting extracellularly or intracellularly [20].
  • 7. Mutation of the glutamate residues responsible for lanthanoid sensitivity of TRPC5 (E543Q and E595Q) modified the potentiation of TRPC5 by acid [21].

Regulatory relationships of TRPC5


Other interactions of TRPC5

  • Functional interaction of the TRPC subunits was verified using a dominant negative TRPC5 mutant (TRPC5DN) [24].
  • 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 [25].
  • We compared its action on SOC activation in a number of cell types and evaluated its modification of three specific TRP channels, canonical transient receptor potential 3 (TRPC3), TRPC5, and TRPV6, to throw light on any link between SOC and TRP channel function [22].
  • Multiple activators of TRPC5 are emerging, including various G protein-coupled receptor agonists, lysophospholipids, lanthanide ions and, in some contexts, calcium store depletion [3].
  • We conclude that in the micromolar range, the lanthanide ions La(3+) and Gd(3+) have opposite effects on whole cell currents through TRPC5 and TRPC6 channels [17].

Analytical, diagnostic and therapeutic context of TRPC5


  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. Canonical Transient Receptor Potential Channels Promote Cardiomyocyte Hypertrophy through Activation of Calcineurin Signaling. Bush, E.W., Hood, D.B., Papst, P.J., Chapo, J.A., Minobe, W., Bristow, M.R., Olson, E.N., McKinsey, T.A. J. Biol. Chem. (2006) [Pubmed]
  3. Canonical transient receptor potential 5. Beech, D.J. Handbook of experimental pharmacology (2007) [Pubmed]
  4. Rapid vesicular translocation and insertion of TRP channels. Bezzerides, V.J., Ramsey, I.S., Kotecha, S., Greka, A., Clapham, D.E. Nat. Cell Biol. (2004) [Pubmed]
  5. TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Strübing, C., Krapivinsky, G., Krapivinsky, L., Clapham, D.E. Neuron (2001) [Pubmed]
  6. Sensing of lysophospholipids by TRPC5 calcium channel. Flemming, P.K., Dedman, A.M., Xu, S.Z., Li, J., Zeng, F., Naylor, J., Benham, C.D., Bateson, A.N., Muraki, K., Beech, D.J. J. Biol. Chem. (2006) [Pubmed]
  7. TRPC5 activation kinetics are modulated by the scaffolding protein ezrin/radixin/moesin-binding phosphoprotein-50 (EBP50). Obukhov, A.G., Nowycky, M.C. J. Cell. Physiol. (2004) [Pubmed]
  8. Block of TRPC5 channels by 2-aminoethoxydiphenyl borate: a differential, extracellular and voltage-dependent effect. Xu, S.Z., Zeng, F., Boulay, G., Grimm, C., Harteneck, C., Beech, D.J. Br. J. Pharmacol. (2005) [Pubmed]
  9. Desensitization of canonical transient receptor potential channel 5 by protein kinase C. Zhu, M.H., Chae, M., Kim, H.J., Lee, Y.M., Kim, M.J., Jin, N.G., Yang, D.K., So, I., Kim, K.W. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  10. TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding. Rao, J.N., Platoshyn, O., Golovina, V.A., Liu, L., Zou, T., Marasa, B.S., Turner, D.J., Yuan, J.X., Wang, J.Y. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  11. A cytosolic residue mediates Mg2+ block and regulates inward current amplitude of a transient receptor potential channel. Obukhov, A.G., Nowycky, M.C. J. Neurosci. (2005) [Pubmed]
  12. Transient receptor potential protein subunit assembly and membrane distribution in human platelets. Brownlow, S.L., Sage, S.O. Thromb. Haemost. (2005) [Pubmed]
  13. mRNA distribution analysis of human TRPC family in CNS and peripheral tissues. Riccio, A., Medhurst, A.D., Mattei, C., Kelsell, R.E., Calver, A.R., Randall, A.D., Benham, C.D., Pangalos, M.N. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  14. Calmodulin and calcium interplay in the modulation of TRPC5 channel activity. Identification of a novel C-terminal domain for calcium/calmodulin-mediated facilitation. Ordaz, B., Tang, J., Xiao, R., Salgado, A., Sampieri, A., Zhu, M.X., Vaca, L. J. Biol. Chem. (2005) [Pubmed]
  15. E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles. Xu, S.Z., Boulay, G., Flemming, R., Beech, D.J. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  16. Cellular localization of TRPC5 in the substantia nigra of rat. De March, Z., Giampà, C., Patassini, S., Bernardi, G., Fusco, F.R. Neurosci. Lett. (2006) [Pubmed]
  17. Lanthanides potentiate TRPC5 currents by an action at extracellular sites close to the pore mouth. Jung, S., Mühle, A., Schaefer, M., Strotmann, R., Schultz, G., Plant, T.D. J. Biol. Chem. (2003) [Pubmed]
  18. Calcium-sensing mechanism in TRPC5 channels contributing to retardation of neurite outgrowth. Hui, H., McHugh, D., Hannan, M., Zeng, F., Xu, S.Z., Khan, S.U., Levenson, R., Beech, D.J., Weiss, J.L. J. Physiol. (Lond.) (2006) [Pubmed]
  19. Human TRPC5 channel activated by a multiplicity of signals in a single cell. Zeng, F., Xu, S.Z., Jackson, P.K., McHugh, D., Kumar, B., Fountain, S.J., Beech, D.J. J. Physiol. (Lond.) (2004) [Pubmed]
  20. Bipolar phospholipid sensing by TRPC5 calcium channel. Beech, D.J. Biochem. Soc. Trans. (2007) [Pubmed]
  21. Potentiation of TRPC5 by protons. Semtner, M., Schaefer, M., Pinkenburg, O., Plant, T.D. J. Biol. Chem. (2007) [Pubmed]
  22. 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]
  23. 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]
  24. Formation of novel TRPC channels by complex subunit interactions in embryonic brain. Strübing, C., Krapivinsky, G., Krapivinsky, L., Clapham, D.E. J. Biol. Chem. (2003) [Pubmed]
  25. Association of immunophilins with mammalian TRPC channels. Sinkins, W.G., Goel, M., Estacion, M., Schilling, W.P. J. Biol. Chem. (2004) [Pubmed]
  26. 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]
  27. Ca2+-calmodulin-dependent myosin light chain kinase is essential for activation of TRPC5 channels expressed in HEK293 cells. Shimizu, S., Yoshida, T., Wakamori, M., Ishii, M., Okada, T., Takahashi, M., Seto, M., Sakurada, K., Kiuchi, Y., Mori, Y. J. Physiol. (Lond.) (2006) [Pubmed]
  28. Molecular cloning and characterization of TRPC5 (HTRP5), the human homologue of a mouse brain receptor-activated capacitative Ca2+ entry channel. Sossey-Alaoui, K., Lyon, J.A., Jones, L., Abidi, F.E., Hartung, A.J., Hane, B., Schwartz, C.E., Stevenson, R.E., Srivastava, A.K. Genomics (1999) [Pubmed]
  29. Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII, and XIV with L- and D-phenylalanine and crystallographic analysis of their adducts with isozyme II: stereospecific recognition within the active site of an enzyme and its consequences for the drug design. Temperini, C., Scozzafava, A., Vullo, D., Supuran, C.T. J. Med. Chem. (2006) [Pubmed]
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