Mammalian TRP Channels.PDF

TRPActivatorsInhibitorsPutative Interacting ProteinsProposed FunctionsC1Activation potentiated by PLC pathwaysGd,LaTRPC4,TRPC5,calmodulin,TRPC3,TRPP1,IP3Rs,caveolin-1,PMCAHomodimer is a purported stretch-sensitive ion channel;form heteromeric ion channels with TRPC4 or TRPC5 in neuronsC2Pheromone receptor mechanism?Calmodulin,IP3R3,Enkurin,TRPC6TRPC2-/-mice respond abnormally to urine-based olfactory cues;pheromone sensingC3Diacylglycerol,Ca2+I,activation potentiated by PLC pathwaysBTP2,flufenamate,Gd,LaTRPC1,calmodulin,PLC,PLC,IP3R,RyR,SERCA,caveolin-1,SNAP,NCX1Potential role in vasoregulation and airway regulationC4La(100 M),calmidazolium,activation potentiated by PLC pathwaysCa2+i,2-APB,niflumic acid,DIDS,La(mM)TRPC1,TRPC5,calmodulin,PLC,NHERF1,IP3RTRPC4-/-mice have abnormalities in endothelial-based vessel permeabilityC5La(100 M),activation potentiated by PLC pathways,nitric oxide2-APB,flufenamate,La(mM)TRPC1,TRPC4,calmodulin,PLC,NHERF1/2,ZO-1,IP3R No phenotype yet reported in TRPC5-/-mice;potentially regulates growth cones and neurite extensionC6Diacylglycerol,Ca2+I,20-HETE,activation potentiated by PLC pathways2-APB,amiloride,Cd,La,GdCalmodulin,TRPC3,TRPC7,FKBP12Missense mutation in human focal segmental glomerulo-sclerosis(FSGS);abnormal vasoregulation in TRPC6-/-mice,proposed role in ATII-induced cardiac hypertrophy C7Diacylglycerol,activation potentiated by PLC pathwaysCa2+I,flufenamate,LaCalmodulin,TRPC3,TRPC6,FKBP12,MxA,TRPC1No phenotype yet reported in TRPC7-/-mice;potential role in myocardial apoptosis V1 T43oC,V-dep,H+,activation potentiated by PLC pathways,anandamide,2-AG,HETE,HPETE,capsaicin,olvanil,resiniferatoxin,ar-vanil,piperine,OEA,2-APB,DPBA,camphorcapsazepine,RuR,acylpolyamines,camphor desensitizesCalmodulin,TRPV3,TRPV2,PI3K,snapin,synaptotagmin IX,-tubulinIn TRPV1-/-mice decreased response to heat,acid pH;diminished stretch-evoked responses in bladder;upregulated in inflammatory bowel disease,osteoarthritisV2 T53oC?,Neuropeptide head activator,DPBA,2-APBRuR,La,SKF96365TRPV1,RGANo phenotype yet reported in TRPV2-/-mice;role in thermal pain,osmosensing in myocytes?V3 T30oC,2-APB,DPBA,carvacrol,thymol,eugenol,camphor,vanillin,ethyl vanillin,menthol,cinnemaldehydeRuR,LaTRPV1TRPV3-/-mice have decreased response to heat;potential role in warmth sensing in skinV4 Anandamide,arachidonic acid,56-ep-oxyeicosatrienoic acids,4-phorbol 12,13 didecanoate,PMA,bisandrographalideRuR,Gd,LaCalmodulin,Src family kinases,aqua-porin 5,pacsin 3TRPV4-/-mice have impaired pressure and acid sensation,dysregulated ADH;potential role in CNS osmosensing and temperature sensing in skinV5 Constitutively active,PIP2Ca2+i,RuR,econazole,CdGdLa,Mg,Cu,PbTRPV6,S100A10/annexin 2,80K-H,NHERF4,BSPRY,Rab11aTRPV5-/-mice have bone abnormalities;possible role in Ca2+uptake in kidney,gutV6 Constitutively activeCa2+i,RuR,CdGdLa,MgTRPV5,S100A10/annexin 2TRPV6-/-mice have alopecia,dermatitis,and decreased intestinal Ca2+reabsorption M1 N.D.N.D.Potential role in melanoma progressionM2 Constitutively active,ADP Ribose,cADP ribose,NAD,H2O2,hypo-osmolarity enhancesADP,N-ACA,econazole,miconazole,clotrimazole,flufenamateCalmodulin,cADP-ribose hydrolase,Sir2Senses oxidant stress in immune cells and glia M3 Constitutively active,hypo-osmolarity enhances,sphingolipids,steroidsMg2+i for M3a1,3a2(9 mM);Gd,LaN.D.Potential role in kidney Ca2+absorptionM4 Ca2+i,decavanadate,BTP2,PKC phosphorylationAMP,ATP,flufenamate,poly-amines;M4a:La,Gd;M4b:free ATP4-i Calmodulin,SUR1TRPM4-/-mice have enhanced anaphylactic responses;potential role in smooth muscle M5 T1R,T2R-Ggus-PLC2,Ca2+i,PIP2,V-dep heat sensitivepH 7.0,spermineN.D.TRPM5-/-mice do not detect sweet,bitter,or umami flavorsM6 Acid pH,2-APBMg2+i,RuRIntegral kinase domain,TRPM7Human TRPM6 mutation causes hypomagnesemia and secondary hypocalcemiaM7 Acid pH,PIP2,activation potentiated by PLC pathwaysMg2+i,La,PIP2 hydrolysisIntegral kinase domain,PLC1,2,3,PLC1,snapin,TRPM6,myosin IIA heavy chain Human TRPM7 variant associated with Guamanian amyo-trophic lateral sclerosis and Parkinson dementia;possible mediator of trace metal entry;role in excitotoxic neuron death M8 T25oC;V-dep,PIP2,menthol,icilin,eucalyptolBCTC,capsazepine,2-APBN.D.Responds to cold and pain;proposed roles in prostate cancer,activation-induced analgesia A1 T18oC?,modification of intracellular cysteines by allyl isothiocyanate,allicin,acrolein,9-THC,carvacrol,icilin,cinnam-aldehyde,eugenol,gingerolRuR,amiloride,camphor,menthol,gentamicin,Gd;carvacrol desensitizesN.D.TRPA1-/-mice have normal hearing;pain defects disputed;responds to pungent natural compounds,environmental irritants,inflammatory peptidesP1 Also called PC2 or PKD2;Mechanical stress,Ca2+i?Gd,La,Cd,SKF96365,2-APB?PKD1/PC1,Hax-1,cortactin,Id2,mDia,troponin,tropomyosin,actinin;cadherin via PKD1/PC1Mutations in human TRPP1 cause Autosomal Dominant Polycystic Kidney Disease(ADPKD);proposed to localize to cilia and be activated by ciliary movementP2 Also called PKD2L1;acid,Ca2+i?flufenamate,Cd,La?PKD1L3TRPP2 is deleted(among other genes)in krd mice that have kidney and retinal abnormalities;mice with targeted deletion in taste cells do not respond to sour(acid)stimuliP3 Also called PKD2L2;Ca2+i?Amiloride,Gd,La,Ni?N.D.Probable function in testisML1 Also called MCOLN1;Ca2+i?Amiloride,Gd,La,Ni?N.D.Mutations in TRPML1 cause mucolipidosis type IV,a reces-sive neurodegenerative lysosomal storage disorder ML2 Also called MCOLN2;N.D.TRPML3 N.D.ML3 MCOLN3;N.D.TRPML1,TRPML2+/-Varitint-waddler mice are deaf with vestibular defectsSnapShot:Mammalian TRP ChannelsDavid E.ClaphamHHMI,Childrens Hospital,Department of Neurobiology,Harvard Medical School,Boston,MA 02115,USA220 Cell 129,April 6,2007 2007 Elsevier Inc.DOI 10.1016/j.cell.2007.03.034 See online version for a list of abbreviations.SnapShot:Mammalian TRP ChannelsDavid E.ClaphamDepartment of Neurobiology,Harvard Medical School,Boston,MA 02115 USA220.e1 Cell 129,April 6,2007 2007 Elsevier Inc.DOI 10.1016/j.cell.2007.03.034AbbreviationsN.D.,not described;TM,transmembrane;V-dep,voltage-dependent.ProteinsSNAP,soluble NSF attachment protein;ATII,Angiotensin II;BSPRY,B box-and SPRY-domain-containing protein;Ca2+/CaM,Calcium-bound calmodulin;FKBP12,FK506-Binding Protein;Gq/11,G protein subunit,type q or 11;Gd,gadolinium;Ggus,G protein gusducin subunit;GPCR,GTP-binding protein-coupled receptor;IP3R,Inositol trisphosphate receptor;La,lanthanum;MxA,interferon-induced 76 kDa GTPase;N-ACA,N-acylase;NCX,Na+/Ca2+exchanger;NHERF/EPB50,Ezrin/moesin/radixin-binding phosphoprotein 50;PDZ,Postsynaptic density/Disc-large/ZO-1 protein domain;PI3K,phosphatidylinositol 3-kinase;PKD,polycystic kidney disease;PLC,Phospholipase C;PMCA,plasma membrane Ca-ATPase transporter;RGA,recombinase gene activator protein;RyR,ryanodine receptor intracellular Ca2+release channel;SERCA,smooth endoplasmic reticulum Ca2+transporter;SUR1,sulfanylurea receptor 1;ZO-1,Zonal Occludens protein 1.Chemicals2-AG,2-arachidonylglycerol;BCTC,(N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide);BTP2,1,3-Bistrifluoromethyl-pyrazole derivative;D9-THC,D9-Tetrahydrocannabinol;DIDS,4,4-DiIsothiocyano-2,2-Stilbene Disulphonic acid;DPBA,Diphenylboronic anhydride;HETE,Hydroxy-Eicosa Tetraenoic Acid;OEA,oleoylethanolamide;PMA,Phorbol 12-Myristate 13-Acetate;RuR,Ruthenium Red.RefeRencesCaterina,M.J.(2007).Transient receptor potential ion channels as participants in thermosensation and thermoregulation.Am.J.Physiol.Regul.Integr.Comp.Physiol.292,R64R76.Clapham,D.E.(2003).TRP channels as cellular sensors.Nature 426,517524.Clapham,D.E.,Owsianik,G.,and Nilius,B.(2007).TRP Ion Channels.IUPHAR Ion Channel Database.http:/clapham.tch.harvard.edu.Desai,C.(2005).TRP channels and mice deficient in TRP channels.Pflugers Arch.451,1118.Dhaka,A.,Viswanath,V.,and Patapoutian,A.(2006).TRP ion channels and temperature sensation.Annu.Rev.Neurosci.29,135161.Montell,C.,Birnbaumer,L.,Flockerzi,V.,Bindels,R.J.,Bruford,E.A.,Caterina,M.J.,Clapham,D.E.,Harteneck,C.,Heller,S.,Julius,D.,et al.(2002).A unified nomen-clature for the superfamily of TRP cation channels.Mol.Cell 9,229231.Nilius,B.,Owsianik,G.,Voets,T.,and Peters,J.A.(2007).Transient receptor potential cation channels in disease.Physiol.Rev.87,165217.Owsianik,G.,DHoedt,D.,Voets,T.,and Nilius,B.(2006).Structure-function relationship of the TRP channel superfamily.Rev.Physiol.Biochem.Pharmacol.156,6190.Owsianik,G.,Talavera,K.,Voets,T.,and Nilius,B.(2006).Permeation and selectivity of TRP channels.Annu.Rev.Physiol.68,685717.Ramsey,I.S.,Delling,M.,and Clapham,D.E.(2006).An introduction to TRP channels.Annu.Rev.Physiol.68,619647.AcknowledgmentsThe author is a scientific advisor for Hydra Biosciences in Cambridge,MA.