Abstract
TRPM5 is a Ca2+-activated cation channel that mediates signaling in taste and other chemosensory cells. Within taste cells, TRPM5 is the final element in a signaling cascade that starts with the activation of G protein-coupled receptors by bitter, sweet, or umami taste molecules and that requires the enzyme PLCĪ²2. PLCĪ²2 breaks down PIP2 into DAG and IP3, and the ensuing release of Ca2+ from intracellular stores activates TRPM5. Since its initial discovery in the taste system, TRPM5 has been found to be distributed in sparse chemosensory cells located throughout the digestive track, in the respiratory system, and in the olfactory system. It is also found in pancreatic islets, where it contributes to insulin secretion. This review highlights recent work on the mechanisms of the activation of the TRPM5 channel and its regulation by voltage, phosphoinositides, temperature, and pH. The distribution of the channel in the body and its functional contribution to various sensory and nonsensory processes are discussed.
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References
Akabas MH, Dodd J, Al-Awqati Q (1988) A bitter substance induces a rise in intracellular calcium in a subpopulation of rat taste cells. Science 242(4881):1047ā1050
Ashcroft FM, Rorsman P (1989) Electrophysiology of the pancreatic beta-cell. Prog Biophys Mol Biol 54(2):87ā143
Ashcroft FM, Harrison DE, Ashcroft SJ (1984) Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells. Nature 312(5993):446ā448
Bernhardt SJ, Naim M, Zehavi U, Lindemann B (1996) Changes in IP3 and cytosolic Ca2+ in response to sugars and non-sugar sweeteners in transduction of sweet taste in the rat. J Physiol 490(Pt 2):325ā336
Bezencon C, Furholz A, Raymond F, Mansourian R, Metairon S, Le Coutre J, Damak S (2008) Murine intestinal cells expressing Trpm5 are mostly brush cells and express markers of neuronal and inflammatory cells. J Comp Neurol 509(5):514ā525. doi:10.1002/cne.21768
Brixel LR, Monteilh-Zoller MK, Ingenbrandt CS, Fleig A, Penner R, Enklaar T, Zabel BU, Prawitt D (2010) TRPM5 regulates glucose-stimulated insulin secretion. Pflugers Arch 460(1):69ā76
Clapham DE (2003) TRP channels as cellular sensors. Nature 426(6966):517ā524
Clapp TR, Stone LM, Margolskee RF, Kinnamon SC (2001) Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction. BMC Neurosci 2:6
Clapp TR, Medler KF, Damak S, Margolskee RF, Kinnamon SC (2006) Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25. BMC Biol 4:7
Colsoul B, Schraenen A, Lemaire K, Quintens R, Van Lommel L, Segal A, Owsianik G, Talavera K, Voets T, Margolskee RF, Kokrashvili Z, Gilon P, Nilius B, Schuit FC, Vennekens R (2010) Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice. Proc Natl Acad Sci USA 107(11):5208ā5213
Colsoul B, Vennekens R, Nilius B (2011) Transient receptor potential cation channels in pancreatic beta cells. Rev Physiol Biochem Pharmacol 161:87ā110. doi:10.1007.112.2011.2
Cook DL, Hales CN (1984) Intracellular ATP directly blocks K+ channels in pancreatic B-cells. Nature 311(5983):271ā273
Dehkordi O, Rose JE, Fatemi M, Allard JS, Balan KV, Young JK, Fatima S, Millis RM, Jayam-Trouth A (2012) Neuronal expression of bitter taste receptors and downstream signaling molecules in the rat brainstem. Brain Res 1475:1ā10
Enklaar T, Esswein M, Oswald M, Hilbert K, Winterpacht A, Higgins M, Zabel B, Prawitt D (2000) Mtr1, a novel biallelically expressed gene in the center of the mouse distal chromosome 7 imprinting cluster, is a member of the Trp gene family. Genomics 67(2):179ā187
Gilon P, Shepherd RM, Henquin JC (1993) Oscillations of secretion driven by oscillations of cytoplasmic Ca2+ as evidences in single pancreatic islets. J Biol Chem 268(30):22265ā22268
Hansen A, Finger TE (2008) Is TrpM5 a reliable marker for chemosensory cells? Multiple types of microvillous cells in the main olfactory epithelium of mice. BMC Neurosci 9:115, 1471-2202-9-115 [pii]
Hille B (2001) Ionic channels of excitable membranes. Sinauer Associates Inc., Sunderland, MA
Hofmann T, Chubanov V, Gudermann T, Montell C (2003) TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel. Curr Biol 13(13):1153ā1158
Huang YA, Roper SD (2010) Intracellular Ca2+ and TRPM5-mediated membrane depolarization produce ATP secretion from taste receptor cells. J Physiol 588(Pt 13):2343ā2350. doi:10.1113/jphysiol.2010.191106, jphysiol.2010.191106 [pii]
Huang L, Shanker YG, Dubauskaite J, Zheng JZ, Yan W, Rosenzweig S, Spielman AI, Max M, Margolskee RF (1999) Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nat Neurosci 2(12):1055ā1062
Hwang PM, Verma A, Bredt DS, Snyder SH (1990) Localization of phosphatidylinositol signaling components in rat taste cells: role in bitter taste transduction. Proc Natl Acad Sci USA 87(19):7395ā7399
Jiang Y, Ruta V, Chen J, Lee A, MacKinnon R (2003) The principle of gating charge movement in a voltage-dependent Kā+āchannel. Nature 423(6935):42ā48
Kaske S, Krasteva G, Konig P, Kummer W, Hofmann T, Gudermann T, Chubanov V (2007) TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells. BMC Neurosci 8:49, 1471-2202-8-49 [pii]
Ketterer C, Mussig K, Heni M, Dudziak K, Randrianarisoa E, Wagner R, Machicao F, Stefan N, Holst JJ, Fritsche A, Haring HU, Staiger H (2011) Genetic variation within the TRPM5 locus associates with prediabetic phenotypes in subjects at increased risk for type 2 diabetes. Metabolism 60(9):1325ā1333. doi:10.1016/j.metabol.2011.02.002, S0026-0495(11)00033-3 [pii]
Kim YS, Kang E, Makino Y, Park S, Shin JH, Song H, Launay P, Linden DJ (2012) Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cells. J Neurophysiol 109(4):1174ā1181, jn.01168.2011 [pii]
Kokrashvili Z, Rodriguez D, Yevshayeva V, Zhou H, Margolskee RF, Mosinger B (2009) Release of endogenous opioids from duodenal enteroendocrine cells requires Trpm5. Gastroenterology 137(2):598ā606, 606.e591ā592
Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP (2002) TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell 109(3):397ā407
Liman ER (2010) A TRP channel contributes to insulin secretion by pancreatic beta-cells. Islets 2(5):331ā333, 12973 [pii]
Liman ER, Corey DP, Dulac C (1999) TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. Proc Natl Acad Sci USA 96(10):5791ā5796
Lin W, Margolskee R, Donnert G, Hell SW, Restrepo D (2007) Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals. Proc Natl Acad Sci USA 104(7):2471ā2476
Lin W, Ezekwe EA Jr, Zhao Z, Liman ER, Restrepo D (2008a) TRPM5-expressing microvillous cells in the main olfactory epithelium. BMC Neurosci 9:114
Lin W, Ogura T, Margolskee RF, Finger TE, Restrepo D (2008b) TRPM5-expressing solitary chemosensory cells respond to odorous irritants. J Neurophysiol 99(3):1451ā1460
Lindemann B (2001) Receptors and transduction in taste. Nature 413(6852):219ā225
Liu D, Liman ER (2003) Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc Natl Acad Sci USA 100(25):15160ā15165
Liu D, Zhang Z, Liman ER (2005) Extracellular acid block and acid-enhanced inactivation of the Ca2+-activated cation channel TRPM5 involve residues in the S3-S4 and S5-S6 extracellular domains. J Biol Chem 280(21):20691ā20699
Liu P, Shah BP, Croasdell S, Gilbertson TA (2011) Transient receptor potential channel type M5 is essential for fat taste. J Neurosci 31(23):8634ā8642. doi:10.1523/JNEUROSCI.6273-10.2011, 31/23/8634 [pii]
Margolskee RF (2002) Molecular mechanisms of bitter and sweet taste transduction. J Biol Chem 277(1):1ā4
McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416(6876):52ā58
Mitrovic S, Nogueira C, Cantero-Recasens G, Kiefer K, Fernandez-Fernandez JM, Popoff JF, Casano L, Bard FA, Gomez R, Valverde MA, Malhotra V (2013) TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells. Elife 2:e00658. doi:10.7554/eLife.0065800658 [pii]
Montell C, Birnbaumer L, Flockerzi V (2002) The TRP channels, a remarkably functional family. Cell 108(5):595ā598
Nilius B, Prenen J, Droogmans G, Voets T, Vennekens R, Freichel M, Wissenbach U, Flockerzi V (2003) Voltage dependence of the Ca2+-activated cation channel TRPM4. J Biol Chem 278(33):30813ā30820
Nilius B, Prenen J, Janssens A, Voets T, Droogmans G (2004) Decavanadate modulates gating of TRPM4 cation channels. J Physiol 560(Pt 3):753ā765
Nilius B, Prenen J, Janssens A, Owsianik G, Wang C, Zhu MX, Voets T (2005a) The selectivity filter of the cation channel TRPM4. J Biol Chem 280(24):22899ā22906
Nilius B, Talavera K, Owsianik G, Prenen J, Droogmans G, Voets T (2005b) Gating of TRP channels: a voltage connection? J Physiol 567(Pt 1):35ā44. doi:10.1113/jphysiol.2005.088377
Ogura T, Mackay-Sim A, Kinnamon SC (1997) Bitter taste transduction of denatonium in the mudpuppy Necturus maculosus. J Neurosci 17(10):3580ā3587
Ogura T, Margolskee RF, Kinnamon SC (2002) Taste receptor cell responses to the bitter stimulus denatonium involve Ca2+ influx via store-operated channels. J Neurophysiol 87(6):3152ā3155
Oike H, Wakamori M, Mori Y, Nakanishi H, Taguchi R, Misaka T, Matsumoto I, Abe K (2006) Arachidonic acid can function as a signaling modulator by activating the TRPM5 cation channel in taste receptor cells. Biochim Biophys Acta 1761(9):1078ā1084
Oka Y, Butnaru M, von Buchholtz L, Ryba NJ, Zuker CS (2013) High salt recruits aversive taste pathways. Nature 494(7438):472ā475. doi:10.1038/nature11905, nature11905 [pii]
Owsianik G, Talavera K, Voets T, Nilius B (2006) Permeation and selectivity of TRP channels. Annu Rev Physiol 68:685ā717. doi:10.1146/annurev.physiol.68.040204.101406
Palmer RK, Atwal K, Bakaj I, Carlucci-Derbyshire S, Buber MT, Cerne R, Cortes RY, Devantier HR, Jorgensen V, Pawlyk A, Lee SP, Sprous DG, Zhang Z, Bryant R (2010) Triphenylphosphine oxide is a potent and selective inhibitor of the transient receptor potential melastatin-5 ion channel. Assay Drug Dev Technol 8(6):703ā713. doi:10.1089/adt.2010.0334
Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A (2002) A TRP channel that senses cold stimuli and menthol. Cell 108(5):705ā715
Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5(11):1169ā1176. doi:10.1038/nn952, nn952 [pii]
Prawitt D, Enklaar T, Klemm G, Gartner B, Spangenberg C, Winterpacht A, Higgins M, Pelletier J, Zabel B (2000) Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression. Hum Mol Genet 9(2):203ā216
Prawitt D, Monteilh-Zoller MK, Brixel L, Spangenberg C, Zabel B, Fleig A, Penner R (2003) TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i. Proc Natl Acad Sci USA 100(25):15166ā15171
Ren Z, Rhyu MR, Phan TH, Mummalaneni S, Murthy KS, Grider JR, Desimone JA, Lyall V (2013) TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response. Am J Physiol Gastrointest Liver Physiol 305(1):G106āG117. doi:10.1152/ajpgi.00053.2013, ajpgi.00053.2013 [pii]
Rohacs T, Lopes CM, Michailidis I, Logothetis DE (2005) PI(4,5)P(2) regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat Neurosci 8(5):626ā634
Shah BP, Liu P, Yu T, Hansen DR, Gilbertson TA (2011) TRPM5 is critical for linoleic acid-induced CCK secretion from the enteroendocrine cell line, STC-1. Am J Physiol Cell Physiol 302(1):C210āC219. doi:10.1152/ajpcell.00209.2011, ajpcell.00209.2011 [pii]
Sturgess NC, Hales CN, Ashford ML (1987) Calcium and ATP regulate the activity of a non-selective cation channel in a rat insulinoma cell line. Pflugers Arch 409(6):607ā615
Suh BC, Hille B (2005) Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate. Curr Opin Neurobiol 15(3):370ā378
Talavera K, Yasumatsu K, Voets T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B (2005) Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature 438(7070):1022ā1025
Talavera K, Yasumatsu K, Yoshida R, Margolskee RF, Voets T, Ninomiya Y, Nilius B (2008) The taste transduction channel TRPM5 is a locus for bitter-sweet taste interactions. FASEB J 22(5):1343ā1355
Ullrich ND, Voets T, Prenen J, Vennekens R, Talavera K, Droogmans G, Nilius B (2005) Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice. Cell Calcium 37(3):267ā278
Vennekens R, Olausson J, Meissner M, Bloch W, Mathar I, Philipp SE, Schmitz F, Weissgerber P, Nilius B, Flockerzi V, Freichel M (2007) Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4. Nat Immunol 8(3):312ā320
Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430(7001):748ā754
Wellman GC, Nelson MT (2003) Signaling between SR and plasmalemma in smooth muscle: sparks and the activation of Ca2+-sensitive ion channels. Cell Calcium 34(3):211ā229
Wong GT, Gannon KS, Margolskee RF (1996) Transduction of bitter and sweet taste by gustducin. Nature 381(6585):796ā800
Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112(3):293ā301, S0092867403000710 [pii]
Zhang Z, Okawa H, Wang Y, Liman ER (2005) Phosphatidylinositol 4,5-Bisphosphate Rescues TRPM4 Channels from Desensitization. J Biol Chem 280(47):39185ā39192
Zhang Z, Zhao Z, Margolskee R, Liman E (2007) The transduction channel TRPM5 is gated by intracellular calcium in taste cells. J Neurosci 27(21):5777ā5786
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Support was provided by the National Institutes of Health, grants R01 DC004564-12 and R21DC012747-01.
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Liman, E.R. (2014). TRPM5. In: Nilius, B., Flockerzi, V. (eds) Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology, vol 222. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54215-2_19
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