Human Transient Receptor Potential Ankyrin 1 Channel: Structure, Function, and Physiology
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, přehledy
- Klíčová slova
- Chemosensation, Gating, Nociception, Sensory transduction, TRPA1 channel, Thermosensation,
- MeSH
- alosterická regulace MeSH
- elektronová kryomikroskopie metody MeSH
- kationtové kanály TRP metabolismus chemie fyziologie MeSH
- kationtový kanál TRPA1 * metabolismus chemie fyziologie MeSH
- lidé MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kationtové kanály TRP MeSH
- kationtový kanál TRPA1 * MeSH
- TRPA1 protein, human MeSH Prohlížeč
The transient receptor potential ion channel TRPA1 is a Ca2+-permeable nonselective cation channel widely expressed in sensory neurons, but also in many nonneuronal tissues typically possessing barrier functions, such as the skin, joint synoviocytes, cornea, and the respiratory and intestinal tracts. Here, the primary role of TRPA1 is to detect potential danger stimuli that may threaten the tissue homeostasis and the health of the organism. The ability to directly recognize signals of different modalities, including chemical irritants, extreme temperatures, or osmotic changes resides in the characteristic properties of the ion channel protein complex. Recent advances in cryo-electron microscopy have provided an important framework for understanding the molecular basis of TRPA1 function and have suggested novel directions in the search for its pharmacological regulation. This chapter summarizes the current knowledge of human TRPA1 from a structural and functional perspective and discusses the complex allosteric mechanisms of activation and modulation that play important roles under physiological or pathophysiological conditions. In this context, major challenges for future research on TRPA1 are outlined.
Zobrazit více v PubMed
Achenbach J, Rhein M, Gombert S et al (2019) Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom. Clin Epigenetics 11(1). https://doi.org/10.1186/s13148-019-0731-0
Akopian AN, Ruparel NB, Jeske NA, Hargreaves KM (2007) Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. J Physiol 583(Pt 1):175–193 PubMed DOI PMC
Anand U, Otto WR, Facer P et al (2008) TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons. Neurosci Lett 438(2):221–227. https://doi.org/10.1016/j.neulet.2008.04.007 PubMed DOI
Andersson DA, Gentry C, Moss S, Bevan S (2008) Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci 28(10):2485–2494. https://doi.org/10.1523/JNEUROSCI.5369-07.2008 PubMed DOI PMC
Andrade EL, Luiz AP, Ferreira J, Calixto JB (2008) Pronociceptive response elicited by TRPA1 receptor activation in mice. Neuroscience 152(2):511–520. https://doi.org/10.1016/j.neuroscience.2007.12.039 PubMed DOI
Andrei SR, Sinharoy P, Bratz IN, Damron DS (2016) TRPA1 is functionally co-expressed with TRPV1 in cardiac muscle: co-localization at z-discs, costameres and intercalated discs. Channels 10(5):395–409. https://doi.org/10.1080/19336950.2016.1185579 PubMed DOI PMC
Anishkin A, Loukin SH, Teng J, Kung C (2014) Feeling the hidden mechanical forces in lipid bilayer is an original sense. Proc Natl Acad Sci 111(22):7898–7905. https://doi.org/10.1073/pnas.1313364111 PubMed DOI PMC
Arenas OM, Zaharieva EE, Para A et al (2017) Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for animal nociception. Nat Neurosci 20(12):1686–1693. https://doi.org/10.1038/s41593-017-0005-0 PubMed DOI PMC
Atoyan R, Shander D, Botchkareva NV (2009) Non-neuronal expression of transient receptor potential type A1 (TRPA1) in human skin. J Investig Dermatol 129(9):2312–2315. https://doi.org/10.1038/jid.2009.58 PubMed DOI
Avenali L, Narayanan P, Rouwette T et al (2014) Annexin A2 regulates TRPA1-dependent nociception. J Neurosci 34(44):14506–14516. https://doi.org/10.1523/JNEUROSCI.1801-14.2014 PubMed DOI PMC
Bahia PK, Parks TA, Stanford KR et al (2016) The exceptionally high reactivity of Cys 621 is critical for electrophilic activation of the sensory nerve ion channel TRPA1. J Gen Physiol 147(6):451–465. https://doi.org/10.1085/jgp.201611581 PubMed DOI PMC
Balestrini A, Joseph V, Dourado M et al (2021) A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment. J Exp Med 218(4). https://doi.org/10.1084/jem.20201637
Bali A, Schaefer SP, Trier I et al (2023) Molecular mechanism of hyperactivation conferred by a truncation of TRPA1. Nat Commun 14(1):2867. https://doi.org/10.1038/s41467-023-38542-1 PubMed DOI PMC
Bamps D, Vriens J, de Hoon J, Voets T (2021) TRP channel cooperation for nociception: therapeutic opportunities. Annu Rev Pharmacol Toxicol 61:655–677. https://doi.org/10.1146/annurev-pharmtox-010919-023238 PubMed DOI
Bandell M, Story GM, Hwang SW et al (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41(6):849–857. https://doi.org/10.1016/s0896-6273(04)00150-3 PubMed DOI
Barvikova K, Barvik I, Sinica V et al (2020) Phospho-mimetic mutation at Ser602 inactivates human TRPA1 channel. Int J Mol Sci 21(21). https://doi.org/10.3390/ijms21217995
Bautista DM, Movahed P, Hinman A et al (2005) Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci U S A 102(34):12248–12252. https://doi.org/10.1073/pnas.0505356102 PubMed DOI PMC
Bautista DM, Jordt SE, Nikai T et al (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124(6):1269–1282. https://doi.org/10.1016/j.cell.2006.02.023 PubMed DOI
Bautista DM, Siemens J, Glazer JM et al (2007) The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448(7150):204–208. https://doi.org/10.1038/nature05910 PubMed DOI
Belinskaia M, Wang J, Kaza SK et al (2023) Bipartite activation of sensory neurons by a TRPA1 agonist allyl isothiocyanate is reflected by complex Ca2+ influx and CGRP release patterns: enhancement by NGF and inhibition with VAMP and SNAP-25 cleaving botulinum neurotoxins. Int J Mol Sci 24(2):1338. https://doi.org/10.3390/ijms24021338 PubMed DOI PMC
Benedikt J, Samad A, Ettrich R et al (2009) Essential role for the putative S6 inner pore region in the activation gating of the human TRPA1 channel. Biochim Biophys Acta 1793(7):1279–1288. https://doi.org/10.1016/j.bbamcr.2009.04.014 PubMed DOI
Bernal L, Sotelo-Hitschfeld P, Konig C et al (2021) Odontoblast TRPC5 channels signal cold pain in teeth. Sci Adv 7(13). https://doi.org/10.1126/sciadv.abf5567
Berrout J, Kyriakopoulou E, Moparthi L et al (2017) TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p. Nat Commun 8(1):947. https://doi.org/10.1038/s41467-017-00983-w PubMed DOI PMC
Bidaye SS, Machacek C, Wu Y, Dickson BJ (2014) Neuronal control of Drosophila walking direction. Science 344(6179):97–101. https://doi.org/10.1126/science.1249964 PubMed DOI
Binder A, May D, Baron R et al (2011) Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients. PLoS One 6(3):e17387. https://doi.org/10.1371/journal.pone.0017387 PubMed DOI PMC
Brackley AD, Gomez R, Guerrero KA et al (2017) A-kinase anchoring protein 79/150 scaffolds transient receptor potential A 1 phosphorylation and sensitization by metabotropic glutamate receptor activation. Sci Rep 7(1):1842. https://doi.org/10.1038/s41598-017-01999-4 PubMed DOI PMC
Cao DS, Zhong L, Hsieh TH et al (2012) Expression of transient receptor potential ankyrin 1 (TRPA1) and its role in insulin release from rat pancreatic beta cells. PLoS One 7(5):e38005. https://doi.org/10.1371/journal.pone.0038005 PubMed DOI PMC
Cao E, Liao M, Cheng Y, Julius D (2013) TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504(7478):113–118. https://doi.org/10.1038/nature12823 PubMed DOI PMC
Chan P, Ding HT, Liederer BM et al (2021) Translational and pharmacokinetic-pharmacodynamic application for the clinical development of GDC-0334, a novel TRPA1 inhibitor. Clin Transl Sci 14(5):1945–1954. https://doi.org/10.1111/cts.13049 PubMed DOI PMC
Chen H, Terrett JA (2020) Transient receptor potential ankyrin 1 (TRPA1) antagonists: a patent review (2015–2019). Expert Opin Ther Patents 30(9):643–657. https://doi.org/10.1080/13543776.2020.1797679 DOI
Chen J, Kang D, Xu J et al (2013) Species differences and molecular determinant of TRPA1 cold sensitivity. Nat Commun 4:2501. https://doi.org/10.1038/ncomms3501 PubMed DOI
Chen Z, Mondal A, Abderemane-Ali F et al (2023) EMC chaperone–CaV structure reveals an ion channel assembly intermediate. Nature. https://doi.org/10.1038/s41586-023-06175-5
Cordero-Morales JF, Gracheva EO, Julius D (2011) Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli. Proc Natl Acad Sci U S A 108(46):E1184–E1191. https://doi.org/10.1073/pnas.1114124108 PubMed DOI PMC
Corey DP, Garcia-Anoveros J, Holt JR et al (2004) TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature 432(7018):723–730. https://doi.org/10.1038/nature03066 PubMed DOI
Cortés-Montero E, Rodríguez-Muñoz M, Ruiz-Cantero MC et al (2021) Calmodulin supports TRPA1 channel association with opioid receptors and glutamate NMDA receptors in the nervous tissue. Int J Mol Sci 22(1):229. https://doi.org/10.3390/ijms22010229 DOI
Dai Y, Wang S, Tominaga M et al (2007) Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J Clin Invest 117(7):1979–1987. https://doi.org/10.1172/JCI30951 PubMed DOI PMC
de Araujo DSM, Nassini R, Geppetti P, De Logu F (2020) TRPA1 as a therapeutic target for nociceptive pain. Expert Opin Ther Targets 24(10):997–1008. https://doi.org/10.1080/14728222.2020.1815191 DOI
de la Roche J, Eberhardt MJ, Klinger AB et al (2013) The molecular basis for species-specific activation of human TRPA1 protein by protons involves poorly conserved residues within transmembrane domains 5 and 6. J Biol Chem 288(28):20280–20292. https://doi.org/10.1074/jbc.M113.479337 PubMed DOI PMC
De Logu F, Nassini R, Materazzi S et al (2017) Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice. Nat Commun 8(1):1887. https://doi.org/10.1038/s41467-017-01739-2 PubMed DOI PMC
Deering-Rice CE, Shapiro D, Romero EG et al (2015) Activation of transient receptor potential Ankyrin-1 by insoluble particulate material and association with asthma. Am J Respir Cell Mol Biol 53(6):893–901. https://doi.org/10.1165/rcmb.2015-0086OC PubMed DOI PMC
del Camino D, Murphy S, Heiry M et al (2010) TRPA1 contributes to cold hypersensitivity. J Neurosci 30(45):15165–15174. https://doi.org/10.1523/JNEUROSCI.2580-10.2010 PubMed DOI PMC
Diver MM, King JVL, Julius D, Cheng Y (2022) Sensory TRP channels in three dimensions. Annu Rev Biochem. https://doi.org/10.1146/annurev-biochem-032620-105738
Dodge K, Scott JD (2000) AKAP79 and the evolution of the AKAP model. FEBS Lett 476(1-2):58–61. https://doi.org/10.1016/s0014-5793(00)01671-9 PubMed DOI
Doerner JF, Gisselmann G, Hatt H, Wetzel CH (2007) Transient receptor potential channel A1 is directly gated by calcium ions. J Biol Chem 282(18):13180–13189. https://doi.org/10.1074/jbc.M607849200 PubMed DOI
Duque M, Lee-Kubli CA, Tufail Y et al (2022) Sonogenetic control of mammalian cells using exogenous transient receptor potential A1 channels. Nat Commun 13(1):600. https://doi.org/10.1038/s41467-022-28205-y PubMed DOI PMC
Earley S, Gonzales AL, Crnich R (2009) Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca PubMed DOI PMC
Egan TJ, Acuna MA, Zenobi-Wong M et al (2016) Effects of N-glycosylation of the human cation channel TRPA1 on agonist-sensitivity. Biosci Rep. https://doi.org/10.1042/BSR20160149
Ehlers MD, Zhang S, Bernhardt JP, Huganir RL (1996) Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit. Cell 84(5):745–755. https://doi.org/10.1016/S0092-8674(00)81052-1 PubMed DOI
El Karim IA, Linden GJ, Curtis TM et al (2011) Human odontoblasts express functional thermo-sensitive TRP channels: implications for dentin sensitivity. Pain 152(10):2211–2223. https://doi.org/10.1016/j.pain.2010.10.016 PubMed DOI
Gallo V, Dijk FN, Holloway JW et al (2017) TRPA1 gene polymorphisms and childhood asthma. Pediatr Allergy Immunol 28(2):191–198. https://doi.org/10.1111/pai.12673 PubMed DOI
Gamper N, Shah S (2022) Inferiority complex: why do sensory ion channels multimerize? Biochem Soc Trans 50(1):213–222. https://doi.org/10.1042/BST20211002 PubMed DOI PMC
Gaudet R (2008) A primer on ankyrin repeat function in TRP channels and beyond. Mol Biosyst 4(5):372–379. https://doi.org/10.1039/b801481g PubMed DOI PMC
Gemmer M, Chaillet ML, van Loenhout J et al (2023) Visualization of translation and protein biogenesis at the ER membrane. Nature 614(7946):160–167. https://doi.org/10.1038/s41586-022-05638-5 PubMed DOI PMC
Gold MG, Stengel F, Nygren PJ et al (2011) Architecture and dynamics of an A-kinase anchoring protein 79 (AKAP79) signaling complex. Proc Natl Acad Sci 108(16):6426–6431. https://doi.org/10.1073/pnas.1014400108 PubMed DOI PMC
Gouin O, L’Herondelle K, Lebonvallet N et al (2017) TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization. Protein Cell 8(9):644–661. https://doi.org/10.1007/s13238-017-0395-5 PubMed DOI PMC
Guo W, Tang Q, Wei M et al (2022) Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites. Neuron 110(6):1023–1035.e1025. https://doi.org/10.1016/j.neuron.2021.12.023 PubMed DOI
Gupta R, Saito S, Mori Y et al (2016) Structural basis of TRPA1 inhibition by HC-030031 utilizing species-specific differences. Sci Rep 6:37460. https://doi.org/10.1038/srep37460 PubMed DOI PMC
Habgood M, Seiferth D, Zaki AM et al (2022) Atomistic mechanisms of human TRPA1 activation by electrophile irritants through molecular dynamics simulation and mutual information analysis. Sci Rep 12(1):4929. https://doi.org/10.1038/s41598-022-08824-7 PubMed DOI PMC
Hall BE, Prochazkova M, Sapio MR et al (2018) Phosphorylation of the transient receptor potential Ankyrin 1 by Cyclin-dependent Kinase 5 affects Chemo-nociception. Sci Rep 8(1):1177. https://doi.org/10.1038/s41598-018-19532-6 PubMed DOI PMC
Hamilton NB, Kolodziejczyk K, Kougioumtzidou E, Attwell D (2016) Proton-gated Ca PubMed DOI PMC
Hasan R, Leeson-Payne AT, Jaggar JH, Zhang X (2017) Calmodulin is responsible for Ca PubMed DOI PMC
Hilton JK, Kim M, Van Horn WD (2019) Structural and evolutionary insights point to allosteric regulation of TRP ion channels. Acc Chem Res 52(6):1643–1652. https://doi.org/10.1021/acs.accounts.9b00075 PubMed DOI PMC
Hinman A, Chuang HH, Bautista DM, Julius D (2006) TRP channel activation by reversible covalent modification. Proc Natl Acad Sci U S A 103(51):19564–19568. https://doi.org/10.1073/pnas.0609598103 PubMed DOI PMC
Hoffmann T, Kistner K, Miermeister F et al (2013) TRPA1 and TRPV1 are differentially involved in heat nociception of mice. Eur J Pain 17(10):1472–1482. https://doi.org/10.1002/j.1532-2149.2013.00331.x PubMed DOI
Hu Z, Zhang Y, Yu W et al (2023) Transient receptor potential ankyrin 1 (TRPA1) modulators: recent update and future perspective. Eur J Med Chem 257:115392. https://doi.org/10.1016/j.ejmech.2023.115392 PubMed DOI
Hynkova A, Marsakova L, Vaskova J, Vlachova V (2016) N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel. Sci Rep 6:28700. https://doi.org/10.1038/srep28700 PubMed DOI PMC
Jabba S, Goyal R, Sosa-Pagan JO et al (2014) Directionality of temperature activation in mouse TRPA1 ion channel can be inverted by single-point mutations in ankyrin repeat six. Neuron 82(5):1017–1031. https://doi.org/10.1016/j.neuron.2014.04.016 PubMed DOI PMC
Jain SM, Balamurugan R, Tandon M et al (2022) Randomized, double-blind, placebo-controlled trial of ISC 17536, an oral inhibitor of transient receptor potential ankyrin 1, in patients with painful diabetic peripheral neuropathy: impact of preserved small nerve fiber function. Pain 163(6):e738–e747. https://doi.org/10.1097/j.pain.0000000000002470 PubMed DOI
Jaquemar D, Schenker T, Trueb B (1999) An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts. J Biol Chem 274(11):7325–7333. https://doi.org/10.1074/jbc.274.11.7325 PubMed DOI
Jhun EH, Hu X, Sadhu N et al (2018) Transient receptor potential polymorphism and haplotype associate with crisis pain in sickle cell disease. Pharmacogenomics 19(5):401–411. https://doi.org/10.2217/pgs-2017-0198 PubMed DOI PMC
Jordt SE, Bautista DM, Chuang HH et al (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427(6971):260–265. https://doi.org/10.1038/nature02282 PubMed DOI
Kadkova A, Synytsya V, Krusek J et al (2017) Molecular basis of TRPA1 regulation in nociceptive neurons. A review. Physiol Res 66(3):425–439. https://doi.org/10.33549/physiolres.933553 PubMed DOI
Kang K, Pulver SR, Panzano VC et al (2010) Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception. Nature 464(7288):597–600. https://doi.org/10.1038/nature08848 PubMed DOI PMC
Karashima Y, Talavera K, Everaerts W et al (2009) TRPA1 acts as a cold sensor in vitro and in vivo. Proc Natl Acad Sci U S A 106(4):1273–1278 PubMed DOI PMC
Khan S, Patra PH, Somerfield H et al (2022) IQGAP1 promotes chronic pain by regulating the trafficking and sensitization of TRPA1 channels. Brain 146(6):2595–2611. https://doi.org/10.1093/brain/awac462 DOI PMC
Kim H, Mittal DP, Iadarola MJ, Dionne RA (2006) Genetic predictors for acute experimental cold and heat pain sensitivity in humans. J Med Genet 43(8):e40. https://doi.org/10.1136/jmg.2005.036079 PubMed DOI PMC
Kittaka H, Tominaga M (2017) The molecular and cellular mechanisms of itch and the involvement of TRP channels in the peripheral sensory nervous system and skin. Allergol Int 66(1):22–30. https://doi.org/10.1016/j.alit.2016.10.003 PubMed DOI
Knowlton WM, Bifolck-Fisher A, Bautista DM, McKemy DD (2010) TRPM8, but not TRPA1, is required for neural and behavioral responses to acute noxious cold temperatures and cold-mimetics in vivo. Pain 150(2):340–350. https://doi.org/10.1016/j.pain.2010.05.021 PubMed DOI PMC
Kochukov MY, McNearney TA, Fu Y, Westlund KN (2006) Thermosensitive TRP ion channels mediate cytosolic calcium response in human synoviocytes. Am J Phys Cell Phys 291(3):C424–C432. https://doi.org/10.1152/ajpcell.00553.2005 DOI
Koivisto A, Jalava N, Bratty R, Pertovaara A (2018) TRPA1 antagonists for pain relief. Pharmaceuticals 11(4). https://doi.org/10.3390/ph11040117
Koivisto AP, Belvisi MG, Gaudet R, Szallasi A (2022) Advances in TRP channel drug discovery: from target validation to clinical studies. Nat Rev Drug Discov 21(1):41–59. https://doi.org/10.1038/s41573-021-00268-4 PubMed DOI
Kremeyer B, Lopera F, Cox JJ et al (2010) A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron 66(5):671–680. https://doi.org/10.1016/j.neuron.2010.04.030 PubMed DOI PMC
Kwan KY, Allchorne AJ, Vollrath MA et al (2006) TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50(2):277–289. https://doi.org/10.1016/j.neuron.2006.03.042 PubMed DOI
Kwan KY, Glazer JM, Corey DP et al (2009) TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J Neurosci 29(15):4808–4819. https://doi.org/10.1523/JNEUROSCI.5380-08.2009 PubMed DOI PMC
Landini L, de Araujo DSM, Titiz M et al (2022) TRPA1 role in inflammatory disorders: what is known so far? Int J Mol Sci 23(9). https://doi.org/10.3390/ijms23094529
Laursen WJ, Bagriantsev SN, Gracheva EO (2014) TRPA1 channels: chemical and temperature sensitivity. Curr Top Membr 74:89–112. https://doi.org/10.1016/B978-0-12-800181-3.00004-X PubMed DOI
Laursen WJ, Anderson EO, Hoffstaetter LJ et al (2015) Species-specific temperature sensitivity of TRPA1. Temperature (Austin) 2(2):214–226. https://doi.org/10.1080/23328940.2014.1000702 PubMed DOI
Li J, Zhang H, Du Q et al (2023) Research progress on TRPA1 in diseases. J Membr Biol. https://doi.org/10.1007/s00232-023-00277-x
Liao M, Cao E, Julius D, Cheng Y (2013) Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504(7478):107–112. https://doi.org/10.1038/nature12822 PubMed DOI PMC
Liu C, Reese R, Vu S et al (2021) A non-covalent ligand reveals biased agonism of the TRPA1 ion channel. Neuron 109(2):273–284.e274. https://doi.org/10.1016/j.neuron.2020.10.014 PubMed DOI
Macikova L, Vyklicka L, Barvik I et al (2019) Cytoplasmic inter-subunit interface controls use-dependence of thermal activation of TRPV3 channel. Int J Mol Sci 20(16). https://doi.org/10.3390/ijms20163990
Marchi M, Salvi E, Andelic M et al (2023) TRPA1 rare variants in chronic neuropathic and nociplastic pain patients. Pain. https://doi.org/10.1097/j.pain.0000000000002905
Marcotti A, Fernandez-Trillo J, Gonzalez A et al (2022) TRPA1 modulation by Sigma-1 receptor prevents oxaliplatin-induced painful peripheral neuropathy. Brain. https://doi.org/10.1093/brain/awac273
Marsakova L, Barvik I, Zima V et al (2017) The first extracellular linker is important for several aspects of the gating mechanism of human TRPA1 channel. Front Mol Neurosci 10:16. https://doi.org/10.3389/fnmol.2017.00016 PubMed DOI PMC
Meents JE, Fischer MJ, McNaughton PA (2017) Sensitization of TRPA1 by protein Kinase A. PLoS One 12(1):e0170097. https://doi.org/10.1371/journal.pone.0170097 PubMed DOI PMC
Meents JE, Ciotu CI, Fischer MJM (2019) TRPA1: a molecular view. J Neurophysiol 121(2):427–443. https://doi.org/10.1152/jn.00524.2018 PubMed DOI
Meng J, Wang J, Steinhoff M, Dolly JO (2016) TNFα induces co-trafficking of TRPV1/TRPA1 in VAMP1-containing vesicles to the plasmalemma via Munc18–1/syntaxin1/SNAP-25 mediated fusion. Sci Rep 6(1):21226. https://doi.org/10.1038/srep21226 PubMed DOI PMC
Mesch S, Walter D, Laux-Biehlmann A et al (2023) Discovery of BAY-390, a selective CNS penetrant chemical probe as transient receptor potential Ankyrin 1 (TRPA1) antagonist. J Med Chem 66(2):1583–1600. https://doi.org/10.1021/acs.jmedchem.2c01830 PubMed DOI PMC
Miyano K, Shiraishi S, Minami K et al (2019) Carboplatin enhances the activity of human transient receptor potential Ankyrin 1 through the cyclic AMP-protein Kinase A-A-Kinase anchoring Protein (AKAP) pathways. Int J Mol Sci 20(13). https://doi.org/10.3390/ijms20133271
Moparthi L, Zygmunt PM (2020) Human TRPA1 is an inherently mechanosensitive bilayer-gated ion channel. Cell Calcium 91. https://doi.org/10.1016/j.ceca.2020.102255
Moparthi L, Survery S, Kreir M et al (2014) Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain. Proc Natl Acad Sci U S A 111(47):16901–16906. https://doi.org/10.1073/pnas.1412689111 PubMed DOI PMC
Moparthi L, Kichko TI, Eberhardt M et al (2016) Human TRPA1 is a heat sensor displaying intrinsic U-shaped thermosensitivity. Sci Rep 6:28763. https://doi.org/10.1038/srep28763 PubMed DOI PMC
Moparthi L, Moparthi SB, Wenger J, Zygmunt PM (2020) Calcium activates purified human TRPA1 with and without its N-terminal ankyrin repeat domain in the absence of calmodulin. Cell Calcium 90:102228. https://doi.org/10.1016/j.ceca.2020.102228 PubMed DOI
Moparthi L, Sinica V, Moparthi VK et al (2022) The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain. Nat Commun 13(1):6113. https://doi.org/10.1038/s41467-022-33876-8 PubMed DOI PMC
Morgan K, Sadofsky LR, Morice AH (2015) Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as ‘well expressed’, ‘poorly expressed’ or ‘salvageable’. Biosci Rep 35(5). https://doi.org/10.1042/BSR20150108
Mukhopadhyay I, Gomes P, Aranake S et al (2011) Expression of functional TRPA1 receptor on human lung fibroblast and epithelial cells. J Recept Signal Transduct Res 31(5):350–358. https://doi.org/10.3109/10799893.2011.602413 PubMed DOI
Nadezhdin KD, Neuberger A, Trofimov YA et al (2021) Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel. Nat Struct Mol Biol 28(7):564–572. https://doi.org/10.1038/s41594-021-00615-4 PubMed DOI PMC
Naert R, Talavera A, Startek JB, Talavera K (2020) TRPA1 gene variants hurting our feelings. Pflugers Arch 472(7):953–960. https://doi.org/10.1007/s00424-020-02397-y PubMed DOI
Naert R, Lopez-Requena A, Talavera K (2021) TRPA1 expression and pathophysiology in immune cells. Int J Mol Sci 22(21). https://doi.org/10.3390/ijms222111460
Nagatomo K, Kubo Y (2008) Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels. Proc Natl Acad Sci U S A 105(45):17373–17378. https://doi.org/10.1073/pnas.0809769105 PubMed DOI PMC
Namer B, Seifert F, Handwerker HO, Maihofner C (2005) TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol. Neuroreport 16(9):955–959. https://doi.org/10.1097/00001756-200506210-00015 PubMed DOI
Nassini R, Pedretti P, Moretto N et al (2012) Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS One 7(8):e42454. https://doi.org/10.1371/journal.pone.0042454 PubMed DOI PMC
Naumov DE, Kotova OO, Gassan DA et al (2021) Effect of TRPM8 and TRPA1 polymorphisms on COPD predisposition and lung function in COPD patients. J Pers Med 11(2). https://doi.org/10.3390/jpm11020108
Nguyen THD, Itoh SG, Okumura H, Tominaga M (2021) Structural basis for promiscuous action of monoterpenes on TRP channels. Commun Biol 4(1):293. https://doi.org/10.1038/s42003-021-01776-0 PubMed DOI PMC
Nikolaev YA, Cox CD, Ridone P et al (2019) Mammalian TRP ion channels are insensitive to membrane stretch. J Cell Sci 132(23). https://doi.org/10.1242/jcs.238360
Nilius B, Appendino G, Owsianik G (2012) The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch 464(5):425–458. https://doi.org/10.1007/s00424-012-1158-z PubMed DOI
Nirenberg MJ, Chaouni R, Biller TM et al (2018) A novel TRPA1 variant is associated with carbamazepine-responsive cramp-fasciculation syndrome. Clin Genet 93(1):164–168. https://doi.org/10.1111/cge.13040 PubMed DOI
Nozawa K, Kawabata-Shoda E, Doihara H et al (2009) TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proc Natl Acad Sci U S A 106(9):3408–3413. https://doi.org/10.1073/pnas.0805323106 PubMed DOI PMC
Nummenmaa E, Hamalainen M, Moilanen LJ et al (2016) Transient receptor potential ankyrin 1 (TRPA1) is functionally expressed in primary human osteoarthritic chondrocytes. Arthritis Res Ther 18(1):185. https://doi.org/10.1186/s13075-016-1080-4 PubMed DOI PMC
Obata K, Katsura H, Mizushima T et al (2005) TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury. J Clin Invest 115(9):2393–2401. https://doi.org/10.1172/JCI25437 PubMed DOI PMC
Oh MH, Oh SY, Lu J et al (2013) TRPA1-dependent pruritus in IL-13-induced chronic atopic dermatitis. J Immunol 191(11):5371–5382. https://doi.org/10.4049/jimmunol.1300300 PubMed DOI
Patil MJ, Salas M, Bialuhin S et al (2020) Sensitization of small-diameter sensory neurons is controlled by TRPV1 and TRPA1 association. FASEB J 34(1):287–302. https://doi.org/10.1096/fj.201902026R PubMed DOI
Paulsen CE, Armache JP, Gao Y et al (2015) Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature 520(7548):511–517. https://doi.org/10.1038/nature14367 PubMed DOI PMC
Pereira I, Mendes SJ, Pereira DM et al (2017) Transient receptor potential Ankyrin 1 channel expression on peripheral blood leukocytes from rheumatoid arthritic patients and correlation with pain and disability. Front Pharmacol 8:53. https://doi.org/10.3389/fphar.2017.00053 PubMed DOI PMC
Prasad P, Yanagihara AA, Small-Howard AL et al (2008) Secretogranin III directs secretory vesicle biogenesis in mast cells in a manner dependent upon interaction with chromogranin A1. J Immunol 181(7):5024–5034. https://doi.org/10.4049/jimmunol.181.7.5024 PubMed DOI
Pumroy RA, Samanta A, Liu Y et al (2019) Molecular mechanism of TRPV2 channel modulation by cannabidiol. eLife 8:e48792. https://doi.org/10.7554/eLife.48792 PubMed DOI PMC
Rosenbaum T, Gordon-Shaag A, Munari M, Gordon SE (2004) Ca2+/calmodulin modulates TRPV1 activation by capsaicin. J Gen Physiol 123(1):53–62 PubMed DOI PMC
Samad A, Sura L, Benedikt J et al (2011) The C-terminal basic residues contribute to the chemical- and voltage-dependent activation of TRPA1. Biochem J 433(1):197–204. https://doi.org/10.1042/BJ20101256 PubMed DOI
Satoh T, Ohba A, Liu Z et al (2015) dPob/EMC is essential for biosynthesis of rhodopsin and other multi-pass membrane proteins in Drosophila photoreceptors. eLife 4:e06306. https://doi.org/10.7554/eLife.06306 PubMed DOI PMC
Sawada Y, Hosokawa H, Hori A et al (2007) Cold sensitivity of recombinant TRPA1 channels. Brain Res 1160:39–46. https://doi.org/10.1016/j.brainres.2007.05.047 PubMed DOI
Schmidt M, Dubin AE, Petrus MJ et al (2009) Nociceptive signals induce trafficking of TRPA1 to the plasma membrane. Neuron 64(4):498–509. https://doi.org/10.1016/j.neuron.2009.09.030 PubMed DOI PMC
Schmidt HR, Zheng S, Gurpinar E et al (2016) Crystal structure of the human σ1 receptor. Nature 532(7600):527–530. https://doi.org/10.1038/nature17391 PubMed DOI PMC
Schmidt HR, Betz RM, Dror RO, Kruse AC (2018) Structural basis for σ1 receptor ligand recognition. Nat Struct Mol Biol 25(10):981–987. https://doi.org/10.1038/s41594-018-0137-2 PubMed DOI PMC
Shigetomi E, Tong X, Kwan KY et al (2011) TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3. Nat Neurosci 15(1):70–80. https://doi.org/10.1038/nn.3000 PubMed DOI PMC
Sinica V, Vlachova V (2021) Transient receptor potential ankyrin 1 channel: an evolutionarily tuned thermosensor. Physiol Res 70(3):363–381. https://doi.org/10.33549/physiolres.934697 PubMed DOI PMC
Sinica V, Zimova L, Barvikova K et al (2019) Human and mouse TRPA1 are heat and cold sensors differentially tuned by voltage. Cells 9(1). https://doi.org/10.3390/cells9010057
Skerratt S (2017) Recent progress in the discovery and development of TRPA1 modulators. Prog Med Chem 56:81–115. https://doi.org/10.1016/bs.pmch.2016.11.003 PubMed DOI
Sleczkowska M, Almomani R, Marchi M et al (2022) Peripheral ion channel genes screening in painful small fiber neuropathy. Int J Mol Sci 23(22). https://doi.org/10.3390/ijms232214095
Song K, Wei M, Guo W et al (2021) Structural basis for human TRPC5 channel inhibition by two distinct inhibitors. eLife 10. https://doi.org/10.7554/eLife.63429
Soriani O, Kourrich S (2019) The Sigma-1 receptor: When adaptive regulation of cell electrical activity contributes to stimulant addiction and cancer. Front Neurosci 13. https://doi.org/10.3389/fnins.2019.01186
Sotomayor M, Corey DP, Schulten K (2005) In search of the hair-cell gating spring elastic properties of ankyrin and cadherin repeats. Structure 13(4):669–682. https://doi.org/10.1016/j.str.2005.03.001 PubMed DOI
Staruschenko A, Jeske NA, Akopian AN (2010) Contribution of TRPV1-TRPA1 interaction to the single channel properties of the TRPA1 channel. J Biol Chem 285(20):15167–15177. https://doi.org/10.1074/jbc.M110.106153 PubMed DOI PMC
Story GM, Peier AM, Reeve AJ et al (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112(6):819–829. https://doi.org/10.1016/s0092-8674(03)00158-2 PubMed DOI
Sulak MA, Ghosh M, Sinharoy P et al (2018) Modulation of TRPA1 channel activity by Cdk5 in sensory neurons. Channels 12(1):65–75. https://doi.org/10.1080/19336950.2018.1424282 PubMed DOI PMC
Suo Y, Wang Z, Zubcevic L et al (2020) Structural insights into electrophile irritant sensing by the human TRPA1 channel. Neuron 105. https://doi.org/10.1016/j.neuron.2019.11.023
Sura L, Zima V, Marsakova L et al (2012) C-terminal Acidic cluster is involved in Ca PubMed DOI PMC
Takahashi N, Kuwaki T, Kiyonaka S et al (2011) TRPA1 underlies a sensing mechanism for O PubMed DOI
Takaishi M, Uchida K, Fujita F, Tominaga M (2014) Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity. J Physiol Sci 64(1):47–57. https://doi.org/10.1007/s12576-013-0289-0 PubMed DOI
Talavera K, Gees M, Karashima Y et al (2009) Nicotine activates the chemosensory cation channel TRPA1. Nat Neurosci 12(10):1293–1299. https://doi.org/10.1038/nn.2379 PubMed DOI
Talavera K, Startek JB, Alvarez-Collazo J et al (2020) Mammalian transient receptor potential TRPA1 channels: from structure to disease. Physiol Rev 100(2):725–803. https://doi.org/10.1152/physrev.00005.2019 PubMed DOI
Talbot BE, Vandorpe DH, Stotter BR et al (2019) Transmembrane insertases and N-glycosylation critically determine synthesis, trafficking, and activity of the nonselective cation channel TRPC6. J Biol Chem 294(34):12655–12669. https://doi.org/10.1074/jbc.RA119.008299 PubMed DOI PMC
Terrett JA, Chen H, Shore DG et al (2021) Tetrahydrofuran-based transient receptor potential Ankyrin 1 (TRPA1) antagonists: ligand-based discovery, activity in a rodent asthma model, and mechanism-of-action via cryogenic electron microscopy. J Med Chem 64(7):3843–3869. https://doi.org/10.1021/acs.jmedchem.0c02023 PubMed DOI
Thakore P, Alvarado MG, Ali S et al (2021) Brain endothelial cell TRPA1 channels initiate neurovascular coupling. Elife 10. https://doi.org/10.7554/eLife.63040
Ufret-Vincenty CA, Klein RM, Hua L et al (2011) Localization of the PIP PubMed DOI PMC
Vandewauw I, De Clercq K, Mulier M et al (2018) A TRP channel trio mediates acute noxious heat sensing. Nature 555(7698):662–666. https://doi.org/10.1038/nature26137 PubMed DOI
Viana F (2016) TRPA1 channels: molecular sentinels of cellular stress and tissue damage. J Physiol 594(15):4151–4169. https://doi.org/10.1113/JP270935 PubMed DOI PMC
Voolstra O, Huber A (2014) Post-translational modifications of TRP channels. Cells 3(2):258–287. https://doi.org/10.3390/cells3020258 PubMed DOI PMC
Wang D, Sadée W, Quillan JM (1999) Calmodulin binding to G protein-coupling domain of opioid receptors. J Biol Chem 274(31):22081–22088. https://doi.org/10.1074/jbc.274.31.22081 PubMed DOI
Wang S, Dai Y, Fukuoka T et al (2008a) Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain. Brain 131(Pt 5):1241–1251. https://doi.org/10.1093/brain/awn060 PubMed DOI
Wang YY, Chang RB, Waters HN et al (2008b) The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions. J Biol Chem 283(47):32691–32703. https://doi.org/10.1074/jbc.M803568200 PubMed DOI PMC
Wang H, Schupp M, Zurborg S, Heppenstall PA (2013) Residues in the pore region of Drosophila transient receptor potential A1 dictate sensitivity to thermal stimuli. J Physiol 591(Pt 1):185–201. https://doi.org/10.1113/jphysiol.2012.242842 PubMed DOI
Wang S, Kobayashi K, Kogure Y et al (2018) Negative regulation of TRPA1 by AMPK in primary sensory neurons as a potential mechanism of painful diabetic neuropathy. Diabetes 67(1):98–109. https://doi.org/10.2337/db17-0503 PubMed DOI
Wang Z, Ye D, Ye J et al (2019) The TRPA1 channel in the cardiovascular system: promising features and challenges. Front Pharmacol 10:1253. https://doi.org/10.3389/fphar.2019.01253 PubMed DOI PMC
Wang X, Li Y, Wei H et al (2023) Molecular architecture and gating mechanisms of the Drosophila TRPA1 channel. Cell Discov 9(1):36. https://doi.org/10.1038/s41421-023-00527-1 PubMed DOI PMC
Weng HJ, Patel KN, Jeske NA et al (2015) Tmem100 is a regulator of TRPA1-TRPV1 complex and contributes to persistent pain. Neuron 85(4):833–846. https://doi.org/10.1016/j.neuron.2014.12.065 PubMed DOI PMC
Wilson SR, Gerhold KA, Bifolck-Fisher A et al (2011) TRPA1 is required for histamine-independent, Mas-related G protein–coupled receptor–mediated itch. Nat Neurosci 14(5):595–602. https://doi.org/10.1038/nn.2789 PubMed DOI PMC
Wright DJ, Simmons KJ, Johnson RM et al (2020) Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site. Commun Biol 3(1):704. https://doi.org/10.1038/s42003-020-01437-8 PubMed DOI PMC
Xiao B, Dubin AE, Bursulaya B et al (2008) Identification of transmembrane domain 5 as a critical molecular determinant of menthol sensitivity in mammalian TRPA1 channels. J Neurosci 28(39):9640–9651. https://doi.org/10.1523/JNEUROSCI.2772-08.2008 PubMed DOI PMC
Yariv B, Yariv E, Kessel A et al (2023) Using evolutionary data to make sense of macromolecules with a “face-lifted” ConSurf. Protein Sci 32(3):e4582. https://doi.org/10.1002/pro.4582 PubMed DOI PMC
Yin Y, Wu M, Zubcevic L et al (2018) Structure of the cold- and menthol-sensing ion channel TRPM8. Science 359(6372):237–241. https://doi.org/10.1126/science.aan4325 PubMed DOI
Zhang X, Li L, McNaughton PA (2008) Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. Neuron 59(3):450–461. https://doi.org/10.1016/j.neuron.2008.05.015 PubMed DOI
Zhang K, Julius D, Cheng Y (2021) Structural snapshots of TRPV1 reveal mechanism of polymodal functionality. Cell 184(20):5138–5150. e5112. https://doi.org/10.1016/j.cell.2021.08.012 PubMed DOI PMC
Zhao C, MacKinnon R (2023) Structural and functional analyses of a GPCR-inhibited ion channel TRPM3. Neuron 111(1):81–91.e87. https://doi.org/10.1016/j.neuron.2022.10.002 PubMed DOI
Zhao J, Lin King JV, Paulsen CE et al (2020) Irritant-evoked activation and calcium modulation of the TRPA1 receptor. Nature 585(7823):141–145. https://doi.org/10.1038/s41586-020-2480-9 PubMed DOI PMC
Zhao Y, McVeigh BM, Moiseenkova-Bell VY (2021) Structural pharmacology of TRP channels. J Mol Biol 433(17):166914. https://doi.org/10.1016/j.jmb.2021.166914 PubMed DOI PMC
Zhou Y, Suzuki Y, Uchida K, Tominaga M (2013) Identification of a splice variant of mouse TRPA1 that regulates TRPA1 activity. Nat Commun 4(1):2399. https://doi.org/10.1038/ncomms3399 PubMed DOI PMC
Zima V, Witschas K, Hynkova A et al (2015) Structural modeling and patch-clamp analysis of pain-related mutation TRPA1-N855S reveal inter-subunit salt bridges stabilizing the channel open state. Neuropharmacology 93:294–307. https://doi.org/10.1016/j.neuropharm.2015.02.018 PubMed DOI
Zimova L, Sinica V, Kadkova A et al (2018) Intracellular cavity of sensor domain controls allosteric gating of TRPA1 channel. Sci Signal 11(514). https://doi.org/10.1126/scisignal.aan8621
Zimova L, Barvikova K, Macikova L et al (2020) Proximal C-terminus serves as a signaling hub for TRPA1 channel regulation via its interacting molecules and supramolecular complexes. Front Physiol 11:189. https://doi.org/10.3389/fphys.2020.00189 PubMed DOI PMC
Zurborg S, Yurgionas B, Jira JA et al (2007) Direct activation of the ion channel TRPA1 by Ca PubMed DOI
Zygmunt PM, Hogestatt ED (2014) TRPA1. Handb Exp Pharmacol 222:583–630. https://doi.org/10.1007/978-3-642-54215-2_23 PubMed DOI