TRPV4

Transient receptor potential cation channel, subfamily V, member 4
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols TRPV4 ; BCYM3; CMT2C; HMSN2C; OTRPC4; SMAL; SPSMA; SSQTL1; TRP12; VRL2; VROAC
External IDs OMIM: 605427 MGI: 1926945 HomoloGene: 11003 IUPHAR: 510 ChEMBL: 3119 GeneCards: TRPV4 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 59341 63873
Ensembl ENSG00000111199 ENSMUSG00000014158
UniProt Q9HBA0 Q9EPK8
RefSeq (mRNA) NM_001177428 NM_022017
RefSeq (protein) NP_001170899 NP_071300
Location (UCSC) Chr 12:
109.78 – 109.83 Mb		 Chr 5:
114.62 – 114.66 Mb
PubMed search

Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4 gene, co-discovered by,[1][2] see also [3]

This gene encodes TRPV4, initially named vanilloid-receptor related osmotically activated channel (VR-OAC), and OSM9-like transient receptor potential channel, member 4 (OTRPC4),[1][2] a member of the vanilloid subfamily in the transient receptor potential (TRP) superfamily of ion channels.[3][4][5] The encoded protein is a Ca2+-permeable, nonselective cation channel that has been found involved in multiple physiologic functions, dysfunctions and also disease. It functions in the regulation of systemic osmotic pressure by the brain, in vascular function, in liver, intestinal, renal and bladder function, in skin barrier function and response of the skin to ultraviolet-B radiation, in growth and structural integrity of the skeleton, in function of joints, in airway- and lung function, in retinal and inner ear function, and in pain. The channel is activated by osmotic, mechanical and chemical cues. It also responds to thermal changes (warmth). Channel activation can be sensitized by inflammation and injury. Hereditary channelopathy mutations of TRPV4 lead to skeletal dysplasias, premature osteoarthritis, and neurological motor function disorders as a manifestation of a motor neuropathy or spinal muscle atrophy.

Clinical significance

Mutations in the TRPV4 gene are associated with a range of disorders, including brachyolmia type 3, congenital distal spinal muscular atrophy, scapuloperoneal spinal muscular atrophy and subtype 2C of Charcot–Marie–Tooth disease.[6]

Pharmacology

A number of TRPV4 agonists and antagonists have been identified since its discovery.[7] The discovery of unselective modulators (e.g. antagonist Ruthenium Red) was followed by the apparition of more potent (agonist 4aPDD)[8] or selective (antagonist RN-1734)[9] compounds, including some with bioavailability suitable for in vivo pharmacology studies such as agonist GSK1016790A[10] (with ~10 fold selectivity vs TRPV1), and antagonists HC-067047[11] (with ~5 fold selectivity vs hERG and ~10 fold selectivity vs TRPM8) and RN-9893[12] (with ~50 fold selectivity vs TRPM8 and ~10 fold selectivity vs M1).

Interactions

TRPV4 has been shown to interact with MAP7[13] and LYN.[14]

See also

References

  1. 1 2 Liedtke W, Choe Y, Martí-Renom MA, Bell AM, Denis CS, Sali A, Hudspeth AJ, Friedman JM, Heller S (October 2000). "Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor". Cell 103 (3): 525–35. doi:10.1016/S0092-8674(00)00143-4. PMC 2211528. PMID 11081638.
  2. 1 2 Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD (October 2000). "OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity". Nat. Cell Biol. 2 (10): 695–702. doi:10.1038/35036318. PMID 11025659.
  3. 1 2 Clapham DE, Julius D, Montell C, Schultz G (Dec 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100.
  4. ↑ Harteneck C, Plant TD, Schultz G (April 2000). "From worm to man: three subfamilies of TRP channels". Trends Neurosci. 23 (4): 159–66. doi:10.1016/S0166-2236(99)01532-5. PMID 10717675.
  5. ↑ Plant TD, Strotmann R (2007). "TRPV4". Handb Exp Pharmacol 179 (179): 189–205. doi:10.1007/978-3-540-34891-7_11. PMID 17217058.
  6. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 605427
  7. ↑ Vincent F, Duncton MA (2011). "TRPV4 agonists and antagonists". Curr Top Med Chem 11 (17): 2216–26. PMID 21671873.
  8. ↑ Watanabe H, Davis JB, Smart D, Jerman JC, Smith GD, Hayes P, Vriens J, Cairns W, Wissenbach U, Prenen J, Flockerzi V, Droogmans G, Benham CD, Nilius B (April 2002). "Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives". J. Biol. Chem. 277 (16): 13569–77. doi:10.1074/jbc.M200062200. PMID 11827975.
  9. ↑ Vincent F, Acevedo A, Nguyen MT, Dourado M, DeFalco J, Gustafson A, Spiro P, Emerling DE, Kelly MG, Duncton MA (November 2009). "Identification and characterization of novel TRPV4 modulators". Biochem. Biophys. Res. Commun. 389 (3): 490–4. doi:10.1016/j.bbrc.2009.09.007. PMID 19737537.
  10. ↑ Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK, McCafferty GP, Chendrimada TP, Lashinger ES, Gordon E, Evans L, Misajet BA, Demarini DJ, Nation JH, Casillas LN, Marquis RW, Votta BJ, Sheardown SA, Xu X, Brooks DP, Laping NJ, Westfall TD (August 2008). "N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I". J. Pharmacol. Exp. Ther. 326 (2): 432–42. doi:10.1124/jpet.108.139295. PMID 18499743.
  11. ↑ Everaerts W, Zhen X, Ghosh D, Vriens J, Gevaert T, Gilbert JP, Hayward NJ, McNamara CR, Xue F, Moran MM, Strassmaier T, Uykal E, Owsianik G, Vennekens R, De Ridder D, Nilius B, Fanger CM, Voets T (November 2010). "Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis". Proc. Natl. Acad. Sci. U.S.A. 107 (44): 19084–9. doi:10.1073/pnas.1005333107. PMC 2973867. PMID 20956320.
  12. ↑ Wei ZL, Nguyen MT, O'Mahony DJ, Acevedo A, Zipfel S, Zhang Q, Liu L, Dourado M, Chi C, Yip V, DeFalco J, Gustafson A, Emerling DE, Kelly MG, Kincaid J, Vincent F, Duncton MA (2015). "Identification of orally-bioavailable antagonists of the TRPV4 ion-channel". Bioorg. Med. Chem. Lett. 25 (18): 4011–5. doi:10.1016/j.bmcl.2015.06.098. PMID 26235950.
  13. ↑ Suzuki M, Hirao A, Mizuno A (December 2003). "Microtubule-associated [corrected] protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4)". J. Biol. Chem. 278 (51): 51448–53. doi:10.1074/jbc.M308212200. PMID 14517216.
  14. ↑ Xu H, Zhao H, Tian W, Yoshida K, Roullet JB, Cohen DM (Mar 2003). "Regulation of a transient receptor potential (TRP) channel by tyrosine phosphorylation. SRC family kinase-dependent tyrosine phosphorylation of TRPV4 on TYR-253 mediates its response to hypotonic stress". J. Biol. Chem. 278 (13): 11520–7. doi:10.1074/jbc.M211061200. PMID 12538589.

External links

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