The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain
Language English Country Great Britain, England Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
36253390
PubMed Central
PMC9576766
DOI
10.1038/s41467-022-33876-8
PII: 10.1038/s41467-022-33876-8
Knihovny.cz E-resources
- MeSH
- Alanine MeSH
- Ankyrin Repeat * MeSH
- TRPA1 Cation Channel genetics metabolism MeSH
- Humans MeSH
- Tryptophan MeSH
- Thermosensing MeSH
- Hot Temperature * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Alanine MeSH
- TRPA1 Cation Channel MeSH
- TRPA1 protein, human MeSH Browser
- Tryptophan MeSH
TRP channels sense temperatures ranging from noxious cold to noxious heat. Whether specialized TRP thermosensor modules exist and how they control channel pore gating is unknown. We studied purified human TRPA1 (hTRPA1) truncated proteins to gain insight into the temperature gating of hTRPA1. In patch-clamp bilayer recordings, ∆1-688 hTRPA1, without the N-terminal ankyrin repeat domain (N-ARD), was more sensitive to cold and heat, whereas ∆1-854 hTRPA1, also lacking the S1-S4 voltage sensing-like domain (VSLD), gained sensitivity to cold but lost its heat sensitivity. In hTRPA1 intrinsic tryptophan fluorescence studies, cold and heat evoked rearrangement of VSLD and the C-terminus domain distal to the transmembrane pore domain S5-S6 (CTD). In whole-cell electrophysiology experiments, replacement of the CTD located cysteines 1021 and 1025 with alanine modulated hTRPA1 cold responses. It is proposed that hTRPA1 CTD harbors cold and heat sensitive domains allosterically coupled to the S5-S6 pore region and the VSLD, respectively.
Department of Clinical Sciences Malmö Lund University SE 214 28 Malmö Sweden
Wallenberg Centre for Molecular Medicine Linköping University SE 581 83 Linköping Sweden
See more in PubMed
Castillo K, Diaz-Franulic I, Canan J, Gonzalez-Nilo F, Latorre R. Thermally activated TRP channels: molecular sensors for temperature detection. Phys. Biol. 2018;15:021001. PubMed
Garcia-Avila M, Islas LD. What is new about mild temperature sensing? A review of recent findings. Temperature (Austin) 2019;6:132–141. PubMed PMC
Voets T, et al. The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature. 2004;430:748–754. PubMed
Dhaka A, Viswanath V, Patapoutian A. Trp ion channels and temperature sensation. Annu. Rev. Neurosci. 2006;29:135–161. PubMed
Baez D, Raddatz N, Ferreira G, Gonzalez C, Latorre R. Gating of thermally activated channels. Curr. Top. Membr. 2014;74:51–87. PubMed
Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D. TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids. Neuron. 2013;77:667–679. PubMed PMC
Moparthi L, et al. Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain. Proc. Natl Acad. Sci. USA. 2014;111:16901–16906. PubMed PMC
Survery S, et al. The N-terminal ankyrin repeat domain is not required for electrophile and heat activation of the purified mosquito TRPA1 receptor. J. Biol. Chem. 2016;291:26899–26912. PubMed PMC
Zakharian E, Cao C, Rohacs T. Gating of transient receptor potential melastatin 8 (TRPM8) channels activated by cold and chemical agonists in planar lipid bilayers. J. Neurosci. 2010;30:12526–12534. PubMed PMC
Nadezhdin KD, et al. Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel. Nat. Struct. Mol. Biol. 2021;28:564–572. PubMed PMC
Moparthi L, et al. Human TRPA1 is a heat sensor displaying intrinsic U-shaped thermosensitivity. Sci. Rep. 2016;6:28763. PubMed PMC
Brauchi S, Orta G, Salazar M, Rosenmann E, Latorre R. A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels. J. Neurosci. 2006;26:4835–4840. PubMed PMC
Jabba S, et al. Directionality of temperature activation in mouse TRPA1 ion channel can be inverted by single-point mutations in ankyrin repeat six. Neuron. 2014;82:1017–1031. PubMed PMC
Clapham DE, Miller C. A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels. Proc. Natl Acad. Sci. USA. 2011;108:19492–19497. PubMed PMC
Jara-Oseguera A, Islas LD. The role of allosteric coupling on thermal activation of thermo-TRP channels. Biophys. J. 2013;104:2160–2169. PubMed PMC
Diaz-Franulic I, Raddatz N, Castillo K, Gonzalez-Nilo FD, Latorre R. A folding reaction at the C-terminal domain drives temperature sensing in TRPM8 channels. Proc. Natl Acad. Sci. USA. 2020;117:20298–20304. PubMed PMC
Qin F. Demystifying thermal channels: driving a channel both forwards and backwards with a single gear? Biophys. J. 2013;104:2118–2120. PubMed PMC
Gao Y, Cao E, Julius D, Cheng Y. TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature. 2016;534:347–351. PubMed PMC
Liu C, et al. A non-covalent ligand reveals biased agonism of the TRPA1 ion channel. Neuron. 2021;109:273–284 e274. PubMed PMC
Pumroy RA, et al. Molecular mechanism of TRPV2 channel modulation by cannabidiol. Elife. 2019;8:e48792. PubMed PMC
Zubcevic L, et al. Cryo-electron microscopy structure of the TRPV2 ion channel. Nat. Struct. Mol. Biol. 2016;23:180–186. PubMed PMC
Diver MM, Cheng Y, Julius D. Structural insights into TRPM8 inhibition and desensitization. Science. 2019;365:1434–1440. PubMed PMC
Kwon DH, et al. Heat-dependent opening of TRPV1 in the presence of capsaicin. Nat. Struct. Mol. Biol. 2021;28:554–563. PubMed PMC
Sinica V, et al. Human and mouse TRPA1 are heat and cold sensors differentially tuned by voltage. Cells. 2011;9:57. PubMed PMC
Takahashi N, et al. TRPA1 underlies a sensing mechanism for O2. Nat. Chem. Biol. 2011;7:701–711. PubMed
Fricke TC, et al. Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2. Proc. Natl Acad. Sci. USA. 2019;116:24359–24365. PubMed PMC
Moparthi L, et al. Electrophile-induced conformational switch of the human TRPA1 ion channel detected by mass spectrometry. Int. J. Mol. Sci. 2020;21:6667. PubMed PMC
Zhao J, Lin King JV, Paulsen CE, Cheng Y, Julius D. Irritant-evoked activation and calcium modulation of the TRPA1 receptor. Nature. 2020;585:141–145. PubMed PMC
Babes A, et al. Photosensitization in porphyrias and photodynamic therapy involves TRPA1 and TRPV1. J. Neurosci. 2016;36:5264–5278. PubMed PMC
Moparthi L, Moparthi SB, Wenger J, Zygmunt PM. Calcium activates purified human TRPA1 with and without its N-terminal ankyrin repeat domain in the absence of calmodulin. Cell Calcium. 2020;90:102228. PubMed
Moparthi L, Zygmunt PM. Human TRPA1 is an inherently mechanosensitive bilayer-gated ion channel. Cell Calcium. 2020;91:102255. PubMed
Sun X, Zakharian E. Regulation of the temperature-dependent activation of transient receptor potential vanilloid 1 (TRPV1) by phospholipids in planar lipid bilayers. J. Biol. Chem. 2015;290:4741–4747. PubMed PMC
Uchida K, et al. Stimulation-dependent gating of TRPM3 channel in planar lipid bilayers. FASEB J. 2016;30:1306–1316. PubMed PMC
Sawada Y, Hosokawa H, Hori A, Matsumura K, Kobayashi S. Cold sensitivity of recombinant TRPA1 channels. Brain Res. 2007;1160:39–46. PubMed
Karashima Y, et al. TRPA1 acts as a cold sensor in vitro and in vivo. Proc. Natl Acad. Sci. USA. 2009;106:1273–1278. PubMed PMC
Hui K, Liu B, Qin F. Capsaicin activation of the pain receptor, VR1: multiple open states from both partial and full binding. Biophys. J. 2003;84:2957–2968. PubMed PMC
Liu B, Hui K, Qin F. Thermodynamics of heat activation of single capsaicin ion channels VR1. Biophys. J. 2003;85:2988–3006. PubMed PMC
Gorokhov VV, et al. Temperature dependence of tryptophan fluorescence lifetime as an indicator of its microenvironment dynamics. Dokl. Biochem. Biophys. 2021;498:170–176. PubMed
Lange M, et al. Direct zinc finger protein persulfidation by H2 S is facilitated by Zn(2) Angew. Chem. Int. Ed. Engl. 2019;58:7997–8001. PubMed
Vivian JT, Callis PR. Mechanisms of tryptophan fluorescence shifts in proteins. Biophys. J. 2001;80:2093–2109. PubMed PMC
Yang S, et al. A paradigm of thermal adaptation in penguins and elephants by tuning cold activation in TRPM8. Proc. Natl Acad. Sci. USA. 2020;117:8633–8638. PubMed PMC
Hoffmann T, et al. TRPA1 and TRPV1 are differentially involved in heat nociception of mice. Eur. J. Pain. 2013;17:1472–1482. PubMed
Bandell M, et al. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron. 2004;41:849–857. PubMed
Bautista DM, et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 2006;124:1269–1282. PubMed
Koltzenburg M, Lundberg LE, Torebjork HE. Dynamic and static components of mechanical hyperalgesia in human hairy skin. Pain. 1992;51:207–219. PubMed
Merrill AW, Cuellar JM, Judd JH, Carstens MI, Carstens E. Effects of TRPA1 agonists mustard oil and cinnamaldehyde on lumbar spinal wide-dynamic range neuronal responses to innocuous and noxious cutaneous stimuli in rats. J. Neurophysiol. 2008;99:415–425. PubMed
Namer B, Seifert F, Handwerker HO, Maihofner C. TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol. Neuroreport. 2005;16:955–959. PubMed
Sinica V, Vlachova V. Transient receptor potential ankyrin 1 channel: an evolutionarily tuned thermosensor. Physiol. Res. 2021;70:363–381. PubMed PMC
Vandewauw I, et al. A TRP channel trio mediates acute noxious heat sensing. Nature. 2018;555:662–666. PubMed
Yarmolinsky DA, et al. Coding and plasticity in the mammalian thermosensory system. Neuron. 2016;92:1079–1092. PubMed PMC
Kremeyer B, et al. A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron. 2010;66:671–680. PubMed PMC
Talavera K, et al. Mammalian transient receptor potential TRPA1 channels: from structure to disease. Physiol. Rev. 2020;100:725–803. PubMed
Zygmunt PM, Högestätt ED. Trpa1. Handb. Exp. Pharm. 2014;222:583–630. PubMed
del Camino D, et al. TRPA1 contributes to cold hypersensitivity. J. Neurosci. 2010;30:15165–15174. PubMed PMC
Gupta R, et al. Structural basis of TRPA1 inhibition by HC-030031 utilizing species-specific differences. Sci. Rep. 2016;6:37460. PubMed PMC
Story GM, et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003;112:819–829. PubMed
Vriens J, et al. TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron. 2011;70:482–494. PubMed
Berrout J, et al. TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p. Nat. Commun. 2017;8:947. PubMed PMC
Nilius B, Prenen J, Owsianik G. Irritating channels: the case of TRPA1. J. Physiol. 2011;589:1543–1549. PubMed PMC
Lindsey H, Petersen NO, Chan SI. Physicochemical characterization of 1,2-diphytanoyl-sn-glycero-3-phosphocholine in model membrane systems. Biochim. Biophys. Acta. 1979;555:147–167. PubMed
Billen B, et al. Different ligands of the TRPV3 cation channel cause distinct conformational changes as revealed by intrinsic tryptophan fluorescence quenching. J. Biol. Chem. 2015;290:12964–12974. PubMed PMC
Lu X, et al. The acquisition of cold sensitivity during TRPM8 ion channel evolution. Proc. Natl Acad. Sci. USA. 2022;119:e2201349119. PubMed PMC
Bahia PK, et al. The exceptionally high reactivity of Cys 621 is critical for electrophilic activation of the sensory nerve ion channel TRPA1. J. Gen. Physiol. 2016;147:451–465. PubMed PMC
Suo Y, et al. Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel. Neuron. 2020;105:882–894.e5. PubMed PMC
Blair NT, et al. Naturally produced defensive alkenal compounds activate TRPA1. Chem. Senses. 2016;41:281–292. PubMed PMC
Ibarra Y, Blair NT. Benzoquinone reveals a cysteine-dependent desensitization mechanism of TRPA1. Mol. Pharm. 2013;83:1120–1132. PubMed PMC
Chen J, et al. Species differences and molecular determinant of TRPA1 cold sensitivity. Nat. Commun. 2013;4:2501. PubMed PMC
Macikova L, et al. Putative interaction site for membrane phospholipids controls activation of TRPA1 channel at physiological membrane potentials. FEBS J. 2019;286:3664–3683. PubMed
Startek JB, et al. Mouse TRPA1 function and membrane localization are modulated by direct interactions with cholesterol. Elife. 2019;8:e46084. PubMed PMC
Wang H, Schupp M, Zurborg S, Heppenstall PA. Residues in the pore region of Drosophila transient receptor potential A1 dictate sensitivity to thermal stimuli. J. Physiol. 2013;591:185–201. PubMed PMC
Kang K, et al. Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila. Nature. 2012;481:76–80. PubMed PMC
Chuang HH, Lin S. Oxidative challenges sensitize the capsaicin receptor by covalent cysteine modification. Proc. Natl Acad. Sci. USA. 2009;106:20097–20102. PubMed PMC
Kashio M, et al. Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions. Proc. Natl Acad. Sci. USA. 2012;109:6745–6750. PubMed PMC
Susankova K, Tousova K, Vyklicky L, Teisinger J, Vlachova V. Reducing and oxidizing agents sensitize heat-activated vanilloid receptor (TRPV1) current. Mol. Pharm. 2006;70:383–394. PubMed
Miles AJ, Ramalli SG, Wallace BA. DichroWeb, a website for calculating protein secondary structure from circular dichroism spectroscopic data. Protein Sci. 2022;31:37–46. PubMed PMC
Voets T. Quantifying and modeling the temperature-dependent gating of TRP channels. Rev. Physiol. Biochem. Pharm. 2012;162:91–119. PubMed
Latorre, R., Vargas, G., Orta, G. & Brauchi, S. Voltage and Temperature Gating of ThermoTRP Channels. In TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades (Eds. Liedtke, W. B. & Heller, S.) Ch. 21 (CRC Press/Taylor & Francis, Boca Raton (FL), 2007). PubMed
Dittert I, et al. Improved superfusion technique for rapid cooling or heating of cultured cells under patch-clamp conditions. J. Neurosci. Methods. 2006;151:178–185. PubMed