Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Transient Receptor Potential Cation Channel Subfamily C Member 5

  • Jose Miguel Arcas
  • Ana GomisEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101908


Historical Background

TRPC5 is a member of the canonical family of transient receptor potential (TRP) channels, forming a subgroup along with TRPC1 and TRPC4. TRPC5 has been cloned from the mouse (Okada et al. 1998; Philipp et al. 1998), rabbit (Philipp et al. 1998), and humans, lying in the Xq23 region of the latter, a region that contains loci for nonsyndromic mental retardation and two genes implicated in X-linked disorders. The TRPC5 protein forms homomers and heteromers with TRPC1, TRPC3, TRPC4, and TRPC6 (Strubing et al. 2001). Like other members of the TRPC family, TRPC5 is a nonselective cationic channel that permits the flow of calcium, sodium, cesium, and potassium ions, although with greater selectivity for Ca 2+. Cation selectivity varies in the literature, from P Ca 2+/P Na + = 14.3 (Okada et al. 1998) to P Ca 2+/P Na + = 1.79 (Schaefer et al. 2000). When...
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  1. Beech DJ. Characteristics of transient receptor potential canonical calcium-permeable channels and their relevance to vascular physiology and disease. Circ J. 2013;77:570–9.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bezzerides VJ, Ramsey IS, Kotecha S, Greka A, Clapham DE. Rapid vesicular translocation and insertion of TRP channels. Nat Cell Biol. 2004;6:709–20.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Gaunt HJ, Vasudev NS, Beech DJ. Transient receptor potential canonical 4 and 5 proteins as targets in cancer therapeutics. Eur Biophy J. 2016;45:611–20.  https://doi.org/10.1007/s00249-016-1142-1.CrossRefGoogle Scholar
  4. Gomis A, Soriano S, Belmonte C, Viana F. Hypoosmotic- and pressure-induced membrane stretch activate TRPC5 channels. J Physiol. 2008;586:5633–49.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Greka A, Navarro B, Oancea E, Duggan A, Clapham DE. TRPC5 is a regulator of hippocampal neurite length and growth cone morphology. Nat Neurosci. 2003;6:837–45.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Jemal I, Soriano S, Conte AL, Morenilla C, Gomis A. G protein-coupled receptor signalling potentiates the osmo-mechanical activation of TRPC5 channels. Pflugers Arch - Eur J Physiol. 2014;466:1635–46.  https://doi.org/10.1007/s00424-013-1392-z.CrossRefGoogle Scholar
  7. Lau OC, Shen B, Wong CO, Tjong YW, Lo CY, Wang HC, et al. TRPC5 channels participate in pressure-sensing in aortic baroreceptors. Nat Commun. 2016;7:11947.  https://doi.org/10.1038/ncomms11947.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Lembrechts R, Brouns I, Schnorbusch K, Pintelon I, Timmermans JP, Adriaensen D. Neuroepithelial bodies as mechanotransducers in the intrapulmonary airway epithelium: involvement of TRPC5. Am J Respir Cell Mol Biol. 2012;47:315–23.  https://doi.org/10.1165/rcmb.2012-0068OC.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Obukhov AG, Nowycky MC. TRPC5 activation kinetics are modulated by the scaffolding protein ezrin/radixin/moesin-binding phosphoprotein-50 (EBP50). J Cell Physiol. 2004;201:227–35.  https://doi.org/10.1002/jcp.20057.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Okada T, Shimizu S, Wakamori M, Maeda A, Kurosaki T, Takada N, et al. Molecular cloning and functional characterization of a novel receptor-activated TRP Ca2+ channel from mouse brain. JBiolChem. 1998;273:10279–87.Google Scholar
  11. Ordaz B, Tang J, Xiao R, Salgado A, Sampieri A, Zhu MX, et al. Calmodulin and calcium interplay in the modulation of TRPC5 channel activity. Identification of a novel C-terminal domain for calcium/calmodulin-mediated facilitation. JBiolChem. 2005;280:30788–96.Google Scholar
  12. Philipp S, Hambrecht J, Braslavski L, Schroth G, Freichel M, Murakami M, et al. A novel capacitative calcium entry channel expressed in excitable cells. EMBO J. 1998;17:4274–82.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Riccio A, Li Y, Moon J, Kim KS, Smith KS, Rudolph U, et al. Essential role for TRPC5 in amygdala function and fear-related behavior. Cell. 2009;137:761–72.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Schaefer M, Plant TD, Obukhov AG, Hofmann T, Gudermann T, Schultz G. Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5. JBiolChem. 2000;275:17517–26.Google Scholar
  15. Strubing C, Krapivinsky G, Krapivinsky L, Clapham DE. TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron. 2001;29:645–55.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Trebak M, Lemonnier L, DeHaven WI, Wedel BJ, Bird GS, Putney Jr JW. Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels. Pflugers Arch - Eur J Physiol. 2009;457:757–69.  https://doi.org/10.1007/s00424-008-0550-1.CrossRefGoogle Scholar
  17. Xu SZ, Sukumar P, Zeng F, Li J, Jairaman A, English A, et al. TRPC channel activation by extracellular thioredoxin. Nature. 2008;451:69–72.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Yoshida T, Inoue R, Morii T, Takahashi N, Yamamoto S, Hara Y, et al. Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol. 2006;2:596–607.  https://doi.org/10.1038/nchembio821.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Zholos AV. Trpc5. Handb Exp Pharmacol. 2014;222:129–56.  https://doi.org/10.1007/978-3-642-54215-2_6.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Zimmermann K, Lennerz JK, Hein A, Link AS, Kaczmarek JS, Delling M, et al. Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system. Proc Natl Acad Sci USA. 2011;108:18114–9.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Instituto de NeurocienciasUniversidad Miguel Hernández-CSICAlicanteSpain