Jump to content

TRPV4

From Wikipedia, the free encyclopedia
TRPV4
Available structures
PDBOrtholog search:PDBeRCSB
Identifiers
AliasesTRPV4,BCYM3, CMT2C, HMSN2C, OTRPC4, SMAL, SPSMA, SSQTL1, TRP12, VRL2, VROAC, transient receptor potential cation channel subfamily V member 4
External IDsOMIM:605427;MGI:1926945;HomoloGene:11003;GeneCards:TRPV4;OMA:TRPV4 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

59341

63873

Ensembl

ENSG00000111199

ENSMUSG00000014158

UniProt

Q9HBA0

Q9EPK8

RefSeq (mRNA)

NM_001177428
NM_001177431
NM_001177433
NM_021625
NM_147204

NM_022017

RefSeq (protein)

NP_001170899
NP_001170902
NP_001170904
NP_067638
NP_671737

NP_071300

Location (UCSC)Chr 12: 109.78 – 109.83 MbChr 5: 114.76 – 114.8 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Transient receptor potential cation channel subfamily V member 4is an ion channel protein that in humans is encoded by theTRPV4gene.

TheTRPV4gene encodes TRPV4, initially named "vanilloid-receptor related osmotically activated channel" (VR-OAC) and "OSM9-liketransient receptor potentialchannel,member 4 (OTRPC4) ",[5][6]a member of the vanilloid subfamily in thetransient receptor potential(TRP) superfamily ofion channels.[7][8][9]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.

TheTRPV4gene has been co-discovered by W. Liedtke et al.[5]and R. Strotmann et al.[6]

Clinical significance

[edit]

Channelopathymutationsin theTRPV4gene lead to skeletal dysplasias, premature osteoarthritis, and neurological motor function disorders and are associated with a range of disorders, includingbrachyolmiatype 3,congenital distal spinal muscular atrophy,Familial digital arthropathy-brachydactyly (FDAB),[10]scapuloperoneal spinal muscular atrophy,and subtype 2C ofCharcot–Marie–Tooth disease.[11]

Pharmacology

[edit]

A number of TRPV4 agonists and antagonists have been identified since its discovery.[12]The discovery of unselective modulators (e.g. antagonistruthenium red) was followed by the apparition of more potent (agonist 4aPDD)[13]or selective (antagonist RN-1734)[14]compounds, including some with bioavailability suitable for in vivo pharmacology studies such as agonistGSK1016790A[15](with ~10 fold selectivity vs TRPV1), and antagonistsHC-067047[16](with ~5 fold selectivity vs hERG and ~10 fold selectivity vs TRPM8) andRN-9893[17](with ~50 fold selectivity vs TRPM8 and ~10 fold selectivity vs M1).

Resolvin D1 (RvD1), a metabolite of theOmega 3 fatty acid,docosahexaenoic acid,is a member of thespecialized proresolving mediators(SPMs) class of metabolites that function to resolve diverse inflammatory reactions and diseases in animal models and, it is proposed, humans. This SPM also dampens pain perception arising from various inflammation-based causes in animal models. The mechanism behind this pain-dampening effect involves the inhibition of TRPV4, probably (in at least certain cases) by an indirect effect wherein it activates another receptor located on neurons or nearbymicrogliaorastrocytes.CMKLR1,GPR32,FPR2,andNMDA receptorshave been proposed to be the receptors through which a SPM may operate todown-regulateTRPs and thereby pain perception.[18][19][20][21][22]

Interactions

[edit]

TRPV4 has been shown tointeractwithMAP7[23]andLYN.[24]

Implication in Temperature-Dependent Sex Determination in Reptiles

[edit]

TRPV4 has been proposed to be the thermal sensor in gonads ofAlligator mississipiensis,a species withtemperature-dependent sex determination.[25]However the data were over interpreted and TRPV4 is probably not involved in temperature-dependent sex determination due to large overlap of expression at male producing temperature and female producing temperature for example.

See also

[edit]

References

[edit]
  1. ^abcGRCh38: Ensembl release 89: ENSG00000111199–Ensembl,May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000014158–Ensembl,May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^abLiedtke W, Choe Y, Martí-Renom MA, Bell AM, Denis CS, Sali A, et al. (October 2000)."Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor".Cell.103(3): 525–535.doi:10.1016/S0092-8674(00)00143-4.PMC2211528.PMID11081638.
  6. ^abStrotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD (October 2000). "OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity".Nature Cell Biology.2(10): 695–702.doi:10.1038/35036318.PMID11025659.S2CID21148080.
  7. ^Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels".Pharmacological Reviews.57(4): 427–450.doi:10.1124/pr.57.4.6.PMID16382100.S2CID17936350.
  8. ^Harteneck C, Plant TD, Schultz G (April 2000). "From worm to man: three subfamilies of TRP channels".Trends in Neurosciences.23(4): 159–166.doi:10.1016/S0166-2236(99)01532-5.PMID10717675.S2CID41074873.
  9. ^Plant TD, Strotmann R (2007). "TRPV4".Transient Receptor Potential (TRP) Channels.Handbook of Experimental Pharmacology. Vol. 179. pp. 189–205.doi:10.1007/978-3-540-34891-7_11.ISBN978-3-540-34889-4.PMID17217058.
  10. ^Lamandé SR, Yuan Y, Gresshoff IL, Rowley L, Belluoccio D, Kaluarachchi K, et al. (October 2011). "Mutations in TRPV4 cause an inherited arthropathy of hands and feet".Nature Genetics.43(11): 1142–1146.doi:10.1038/ng.945.PMID21964574.S2CID27430401.
  11. ^Online Mendelian Inheritance in Man(OMIM):605427
  12. ^Vincent F, Duncton MA (2011). "TRPV4 agonists and antagonists".Current Topics in Medicinal Chemistry.11(17): 2216–2226.doi:10.2174/156802611796904861.PMID21671873.
  13. ^Watanabe H, Davis JB, Smart D, Jerman JC, Smith GD, Hayes P, et al. (April 2002)."Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives".The Journal of Biological Chemistry.277(16): 13569–13577.doi:10.1074/jbc.M200062200.PMID11827975.
  14. ^Vincent F, Acevedo A, Nguyen MT, Dourado M, DeFalco J, Gustafson A, et al. (November 2009). "Identification and characterization of novel TRPV4 modulators".Biochemical and Biophysical Research Communications.389(3): 490–494.doi:10.1016/j.bbrc.2009.09.007.PMID19737537.
  15. ^Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK, McCafferty GP, et al. (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".The Journal of Pharmacology and Experimental Therapeutics.326(2): 432–442.doi:10.1124/jpet.108.139295.PMID18499743.S2CID517735.
  16. ^Everaerts W, Zhen X, Ghosh D, Vriens J, Gevaert T, Gilbert JP, et al. (November 2010)."Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis".Proceedings of the National Academy of Sciences of the United States of America.107(44): 19084–19089.Bibcode:2010PNAS..10719084E.doi:10.1073/pnas.1005333107.PMC2973867.PMID20956320.
  17. ^Wei ZL, Nguyen MT, O'Mahony DJ, Acevedo A, Zipfel S, Zhang Q, et al. (September 2015). "Identification of orally-bioavailable antagonists of the TRPV4 ion-channel".Bioorganic & Medicinal Chemistry Letters.25(18): 4011–4015.doi:10.1016/j.bmcl.2015.06.098.PMID26235950.
  18. ^Qu Q, Xuan W, Fan GH (January 2015). "Roles of resolvins in the resolution of acute inflammation".Cell Biology International.39(1): 3–22.doi:10.1002/cbin.10345.PMID25052386.S2CID10160642.
  19. ^Serhan CN, Chiang N, Dalli J, Levy BD (October 2014)."Lipid mediators in the resolution of inflammation".Cold Spring Harbor Perspectives in Biology.7(2): a016311.doi:10.1101/cshperspect.a016311.PMC4315926.PMID25359497.
  20. ^Lim JY, Park CK, Hwang SW (2015)."Biological Roles of Resolvins and Related Substances in the Resolution of Pain".BioMed Research International.2015:830930.doi:10.1155/2015/830930.PMC4538417.PMID26339646.
  21. ^Ji RR, Xu ZZ, Strichartz G, Serhan CN (November 2011)."Emerging roles of resolvins in the resolution of inflammation and pain".Trends in Neurosciences.34(11): 599–609.doi:10.1016/j.tins.2011.08.005.PMC3200462.PMID21963090.
  22. ^Serhan CN, Chiang N, Dalli J (May 2015)."The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution".Seminars in Immunology.27(3): 200–215.doi:10.1016/j.smim.2015.03.004.PMC4515371.PMID25857211.
  23. ^Suzuki M, Hirao A, Mizuno A (December 2003)."Microtubule-associated [corrected] protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4)".The Journal of Biological Chemistry.278(51): 51448–51453.doi:10.1074/jbc.M308212200.PMID14517216.
  24. ^Xu H, Zhao H, Tian W, Yoshida K, Roullet JB, Cohen DM (March 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".The Journal of Biological Chemistry.278(13): 11520–11527.doi:10.1074/jbc.M211061200.PMID12538589.
  25. ^Yatsu R, Miyagawa S, Kohno S, Saito S, Lowers RH, Ogino Y, Fukuta N, Katsu Y, Ohta Y, Tominaga M, Guillette LJ, Iguchi T (2015)."TRPV4 associates environmental temperature and sex determination in the American alligator".Sci Rep.5:18581.Bibcode:2015NatSR...518581Y.doi:10.1038/srep18581.PMC4683465.PMID26677944.
[edit]

This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.

Retrieved from "https://en.wikipedia.org/w/index.php?title=TRPV4&oldid=1234954937"