Transient Receptor Potential channels (TRP) in GtoPdb v.2023.1

The TRP superfamily of channels (nomenclature as agreed by NC-IUPHAR [176, 1072]), whose founder member is the Drosophila Trp channel, exists in mammals six families; TRPC, TRPM, TRPV, TRPA, TRPP and TRPML based on amino acid homologies. subunits contain putative TM domains assemble homo- or hetero-tetramers to form cation selective with diverse modes activation varied permeation properties (reviewed [730]). Established, potential, physiological functions individual members families are discussed detail recommended reviews a number books [401, 686, 1155, 256]. established, involvement disease [1126] reviewed [448, 685], [688] [464], together special edition Biochemica et Biophysica Acta subject [685]. Additional related reviews, for pain [633], stroke [1135], sensation inflammation [988], itch [130], airway [310, 1051], available. pharmacology most has been advanced recent years. Broad spectrum agents listed tables along more selective, recently recognised, ligands that flagged inclusion primary reference. See Rubaiy (2019) review pharmacological tools TRPC1/C4/C5 [805]. Most regulated phosphoinostides such PtIns(4,5)P2 although effects reported often complex, occasionally contradictory, likely be dependent upon experimental conditions, intracellular ATP levels [1009, 689, 801]). Such regulation generally not included tables.When thermosensitivity mentioned, it refers specifically high Q10 gating, range 10-30, but does necessarily imply channel's function act 'hot' 'cold' sensor. In general, search activators led many claims temperature sensing, mechanosensation, lipid sensing. All proteins course sensitive energies binding, mechanical force, temperature, issue whether proposed input within physiologically relevant resulting response. TRPA (ankyrin) familyTRPA1 sole mammalian this group [293]). TRPA1 sensory neurons contribute nociception [414, 890, 602]. Pungent chemicals mustard oil (AITC), allicin, cinnamaldehyde activate modification free thiol groups cysteine side chains, especially those located its terminus [575, 60, 365, 577]. Alkenals α, β-unsaturated bonds, propenal (acrolein), butenal (crotylaldehyde), 2-pentenal can react thiols via Michael addition TRPA1. However, potency appears weaken carbon chain length increases [26, 60]. Covalent leads sustained Chemicals including carvacrol, menthol, local anesthetics reversibly non-covalent binding [424, 511, 1081, 1080]. mechanosensitive under activated cold temperatures [425, 212]. electron cryo-EM structure [740] indicates 6-TM homotetramer. Each subunit channel contains two short ‘pore helices’ pointing into ion selectivity filter, which big enough allow partially hydrated Ca2+ ions. TRPC (canonical) familyMembers subfamily [284, 778, 18, 4, 94, 446, 739, 70]) fall subgroups outlined below. TRPC2 pseudogene humans. It accepted all downstream Gq/11-coupled receptors, receptor tyrosine kinases [765, 953, 1072]). A comprehensive listing G-protein coupled receptors given [4]. Hetero-oligomeric complexes their association signalling detailed [18] [447]. have frequently store-operated (SOCs) (or compenents mulimeric SOCs), depletion calcium stores [741, 770, 820, 1121, 157, 726, 64, 158]). weight evidence they directly gated conventional mechanisms, established Stim-gated Orai channels. mechanically ranges force. family blocked 2-APB SKF96365 [347, 346]. Activation lipids [70]. Important progress made [805, 619, 436, 102, 851, 191, 291]. regulate variety implicated human diseases [295, 71, 885, 1031, 1025, 154, 103, 561, 913, 409]. subgroup TRPC1 alone may functional [229]. TRPC4/C5 distinguished from other potentiation micromolar concentrations La3+. humans, an localized microvilli vomeronasal organ. required normal sexual behavior response pheromones mice. also main olfactory epithelia mice [1114, 723, 724, 1115, 539, 1168, 1109].TRPC3/C6/C7 diacylglycerol independent protein kinase C stimulation [347].TRPM (melastatin) TRPM [275, 346, 741, 1151]) five TRPM1/M3 subgroupIn darkness, glutamate released photoreceptors ON-bipolar cells binds metabotropic 6 , leading Go . This results closure TRPM1. When stimulated light, release reduced, TRPM1 active, cell membrane depolarization. Human mutations associated congenital stationary night blindness (CSNB), patients lack rod function. found melanocytes. Isoforms present melanocytes, melanoma, brain, retina. melanoma cells, prevalent highly dynamic vesicular structures [398, 708]. TRPM3 [714]) multiple splice variants differ significantly biophysical properties. expressed somatosensory important development heat hyperalgesia during (see [941]). coexpressed TRPV1 these neurons. pancreatic beta well pituitary gland, eye, kidney, adipose tissue [713, 940]. detection noxious [1017]. TRPM2TRPM2 conditions oxidative stress (respiratory burst phagocytic cells). direct calcium, adenosine diphosphate ribose (ADPR) [970] cyclic ADPR (cADPR) [1118]. As channels, PI(4,5)P2 must [1109]. Numerous TRPM2 exist mechanisms [239]. Recent studies (hs) TRPM2, demonstrate sites hsTRPM2, one N-terminal MHR1/2 domain C-terminal NUDT9-H domain. addition, site S2-S3 loop revealed mediate induces conformational changes ADPR-bound closed open [387, 1027]. Meanwhile, quadruple-residue motif (979FGQI982) was identified filter gate control hsTRPM2 [1120]. involved warmth [848], contributes several [76]. interacts extra synaptic NMDA (NMDAR) enhances NMDAR activity ischemic [1164]. macrophages promotes atherosclerosis [1165, 1147]. Moreover, silica nanoparticles induce lung ROS/PARP/TRPM2 signaling-mediated lysosome impairment autophagy dysfunction [1028]. designed various compounds potential selectively inhibit ACA derivatives A23, 2,3-dihydroquinazolin-4(1H)-one [1137, 1139]. TRPM4/5 subgroupTRPM4 TRPM5 distinction being impermeable [1072]. variant TRPM4 (i.e.TRPM4b) molecular candidates endogenous calcium-activated (CAN) [327]. active late phase repolarization cardiac ventricular action potential. deletion knockout adrenergic-mediated inotropy [593]. Mutations conduction defects [404, 593, 879]. shown regulator entry mast [993] dendritic migration [52]. taste tongue essential transduction sweet, bitter stimuli [537] slow afterdepolarization layer 5 mouse prefrontal cortex [513]. Both [246]. TRPM6/7 subgroupTRPM6 7 combine enzymatic activities (‘chanzymes’) [172]. These unusual property divalent (Ca2+, Mg2+, Zn2+) monovalent cations, single conductances, overall extremely small inward conductance when plasma membrane. They inhibited internal Mg2+ at ~0.6 mM, around level cells. Whether homeostasis contentious issue. PIP2 TRPM6 TRPM7 [810, 1077]. either gene deleted mice, result embryonic lethality [413, 1065]. region cleaved unknown stimuli, phosphorylates nuclear histones [479, 480]. responsible oxidant- induced Zn2+ vesicles [3] intestinal mineral absorption postnatal survival [622]. metal transporter CNNM1-4 interact [40, 467]. TRPM8Is cooling evoking ‘cool’ participates thermosensation [63, 178, 224] [1011, 562, 457, 649]. Direct chemical agonists include menthol icilin[1086]. Besides, linalool promote ERK phosphorylation dermal microvascular endothelial down-regulate levels, TRPM8 [68]. typical S4-S5 connectomes clear filters exowell rings [512], cryo-electron microscopy closed, intermediate, states ligand- PIP2-dependent pathways [1111]. last 36 acids carboxyl terminal key sequences TRPM8's temperature-sensitive [194]. deficiency reduced expression S100A9 increased HNF4α liver fibrosis progression fibrosis, helped alleviate symptoms bile duct [556]. Channel shortens time hypersensitivity reactions migraine models promoting recovery sensitivity [12]. peptide DeC‐1.2 ligand activation, eliminate dysalgesia oxaliplatin-treated without changing body [9]. Analysis clinical data shows TRPM8-specific blockers WS12 reduce tumor growth colorectal cancer xenografted reducing transcription Wnt signaling regulators β-catenin target oncogenes, C-Myc Cyclin D1 [732]. (mucolipin) familyThe [782, 1132, 775, 1084, 190] consists three (TRPML1-3). probably restricted (MCOLN1) encoding TRPML1 (mucolipin-1) cause neurodegenerative disorder mucolipidosis type IV (MLIV) man. sorting/transport endosomes endocytotic pathway specifically, fission endosome-lysosome hybrid lysosomal exocytosis [822]. TRPML2 TRPML3 show low luminal sodium and/or pH, similar molecules [319, 147, 877]. naturally occurring gain mutation (i.e. A419P) varitint waddler (Va) phenotype 690]). (polycystin) [216, 214, 300, 1061, 374]) PKD2 comprised (PC2), PKD2L1 (PC2L1), PKD2L2 (PC2L2), renamed TRPP1, TRPP2 TRPP3, respectively should noted nomenclature PC2 old literature. uniformed called [345]. clearly distinct PKD1 family, unknown. hetero-oligomeric complex 1:3 ratio. [905]. Although still sorted out, appear 6TM spanning nonselective TRPV (vanilloid) [995]) broadly divided non-selective TRPV1-4 TRPV5 TRPV6. TRPV1-V4 subfamilyTRPV1 thermal following noxius [762, 882, 922]). described, some modulate TRPV1, dominant negative manner co-expressed [844]. [329] [1015]. TRPV2 thermosensor man [736], innate immunity [547]. Functional described placental trophoblast [204]. TRPV3 TRPV4 both thermosensitive. There mechanosensitive, native environment [127, 530]. TRPV5/V6 TRPV6 placenta, bone, kidney. Under reabsorption across kidney tubule [1057, 205, 651, 270]).TRPV6 play role transport placenta [1056].