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It is assumed that the gastrointestinal and the respiratory tracts have the ability to analyze the composition of their luminal content in order to adequately respond to toxins and irritants. Thus, signaling molecules enriched in TRC have also been identified in populations of solitary epithelial cells in organs other than taste buds. For example, Gαgust was found in brush cells of the gastrointestinal tract and in pancreatic duct cells [23, 24]. Bitter taste receptors, T2Rs, Gαgust, PLCβ2 and the IP3III receptor were immunolocalized in solitary chemosensory cells (SCC) in the larynx and respiratory epithelium [2528]. Gαgust was found to be expressed in L type enteroendocrine cells in the human colon [29]. These observations support the notion that a population of specialized epithelial cells is present in different organs and may constitute part of a diffuse chemosensory system [30, 31]. At present, common functional, morphological and biochemical criteria defining this putative cell system or these systems are not available and are the subject of intensive investigation.



Localization of TRPM5 on the basolateral surface of taste receptor cells


Figure 1

Immunolocalization of TRPM5 in taste buds of mouse papillae vallatae. The TRPM5-specific antibody Ab-321 recognizes TRPM5 transiently expressed in HEK 293 cells. (A) Western blot analysis of total lysates of mock- (line 1), TRPM5- (line 2) and YFP-TRPM5- (line 3) transfected HEK 293 cells. Positions of TRPM5- and YFP-TRPM5-specific bands are indicated by arrowheads. (B) Overlay of confocal and corresponding differential interference contrast (DIC) images of immunofluorescence staining of HEK 293 cells transiently expressing wild-type TRPM5. (C-E) Immunohistochemistry of taste buds using a TRPM5-specific antibody at lower (C) and higher magnifications (D, E). Notably, TRPM5 is predominantly localized on the basolateral surface of cells (indicated by the arrow in (D, E)). (F) Lack of TRPM5 immunoreactivity in taste receptors after preincubation of the TRPM5-specific antibody with the immunization peptide. (G-I) Fluorescent labeling of taste buds with the TRPM5-specific antibody (E) and the UEA lectin (H) and overlay of both with corresponding DIC image (I). Note that only a subset of cells in the taste bud is enriched in TRPM5. In the TRPM5-positive cells, TRPM5 is mainly localized on the basolateral cell surface and absent in microvilli (as indicated by an arrow (G, H, I)). Scale bars are 20 μm each.


Expression of TRPM5 in chemosensory organs



Figure 2

TRPM5 expression in mouse main olfactory epithelium and the vomeronasal organ. Confocal images of TRPM5-specific signals (left panels) and overlay with corresponding DIC images (right panel) are depicted. (A-D) Immunolocalization of TRPM5 in solitary cells of the main olfactory epithelium is shown at lower (indicated by the arrows in (A, B)) and higher magnifications (C, D). (E-H) Immunohistochemistry of TRPM5 in the VNO. (E, F) Localization of TRPM5 on the apical surface of sensory epithelia (indicated by the arrow). (G, H) Detection of TRPM5-enriched solitary cells in the non-sensory part of the VNO. Scale bars are 20 μm.


TRPM5 is enriched in brush cells of the respiratory system

By means of RT-PCR and Northern blot analysis, TRPM5 expression has been demonstrated in many tissues [33, 34]. Therefore, we systematically searched rodent organs for TRPM5 protein expression by immunohistochemistry. TRPM5 could not be detected in liver, pancreas, kidney, spleen, lymph nodes, vessels, salivary glands, ovary, blood cells, fat cells, skeletal and smooth muscle (data not shown). We did, however, observe TRPM5 immunoreactive cells in the respiratory system (Figure 3) as well as in the gastrointestinal tract (Figures 4, 5).

Figure 3

TRPM5 is specifically expressed in brush cells of the respiratory system. Detection of solitary TRPM5-expressing cells in the mouse respiratory epithelium of nose (indicated by arrows in (A)), trachea (B) and bronchus (C). Overlays of TRPM5 fluorescence with the corresponding DIC images are shown. The inset in (C) shows the fluorescent image of a TRPM5-positive cell with a basolateral extension (indicated by the arrow). (D-L) TRPM5-expressing cells express brush cell-specific marker proteins. Confocal images of TRPM5-specific signals (left panels), villin or CK18 (middle panels) and their overlays with corresponding DIC images (right panel) are shown. Note the co-localization of TRPM5 with villin (D-F) and CK18 (G-H) in rat trachea and TRPM5 with villin in rat alveolar epithelium (J-L). Scale bars are 20 μm.

Figure 4

Distribution of TRPM5-immunoreactive cells in the mouse gastrointestinal tract. Confocal images of TRPM5-specific signals (left panel) and their overlay with the corresponding DIC images (right panel) are depicted. (A, B) TRPM5-expressing cells are abundant in the cardiac region of the stomach. In gut epithelia, TRPM5-enriched cells are detected in the duodenal villi (C, D), the ileum (E, F) and the colon (G, H). Scale bars are 20 μm.

Figure 5



The distribution and morphological characteristics of these TRPM5-expressing cells were indicative of neuroendocrine cells, neuroendocrine bodies or brush cells [3537]. In order to assign the TRPM5-expressing cells to one of these entities, we performed double immunostainings against TRPM5 and cell-specific markers.


Localization of TRPM5 in the gastrointestinal tract











It was recently postulated that a population of specialized cells of the respiratory epithelium and gastrointestinal tract forming the so-called diffuse chemosensory system participates in the recognition and processing of diverse environmental cues [30, 54]. This assumption was recently substantiated by the immunolocalization of signaling proteins such as Gαgust, T2R, PLCβ2 and the IP3III receptor in solitary intestinal epithelial cells and in cells of the respiratory system.)[23, 2529, 55]. In accordance with these earlier findings, Bezençon et al. took advantage of TRPM5 promoter-based eGFP transgenic mice and identified GFP-positive cells in the gastrointestinal tract which partially co-express a set of taste signaling proteins mentioned above [56].


Brush cells were initially defined by morphological criteria, and a clear biological role of this cell population still remains elusive. Hypotheses about these cells' functional role range from absorptive processes [57], mechanosensation [58], secretion [5961] or a contribution to the local immunological defense barrier [6266]. In the respiratory system and the gastrointestinal tract, brush cells may play a role in sensation of chemical compounds in the lumen [23, 24, 35, 39, 6769]. The latter notion is derived from two salient observations: Firstly, brush cells display morphological features similar to TRC. Both cell types are characterized by an apical tuft of stiff microvilli with long rootlets into the cytoplasm lacking classical exocytotic vesicles or synapses [8, 17, 30, 40]. Secondly, several signaling proteins pertinent to taste perception were identified in a subset of brush cells, including α-gustducin [23, 24] and NO-synthase [70]. To our knowledge, TRPM5 is the first protein identified to be specifically expressed in brush cells of the gastrointestinal tract and the respiratory system. These results lend further support to the view that taste cells and brush cells share a common functional principle, i.e. chemosensation, and that brush cells are an important cellular correlate for chemosensation in the periphery.




Antibodies and chemicals






Cell culture, Western blot analysis and immunocytochemistry on cells




Immunohistochemistry on tissue sections




Confocal microscopy



  1. 1.

    Dhaka A, Viswanath V, Patapoutian A: TRP Ion Channels and Temperature Sensation. Annu Rev Neurosci. 2006, 29: 135-161. 10.1146/annurev.neuro.29.051605.112958.

  2. 2.

    Ramsey IS, Delling M, Clapham DE: An introduction to TRP channels. Annu Rev Physiol. 2006, 68: 619-647. 10.1146/annurev.physiol.68.040204.100431.

  3. 3.

    Liman ER, Corey DP, Dulac C: TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. Proc Natl Acad Sci U S A. 1999, 96 (10): 5791-5796. 10.1073/pnas.96.10.5791.

  4. 4.

    Stowers L, Holy TE, Meister M, Dulac C, Koentges G: Loss of sex discrimination and male-male aggression in mice deficient for TRP2. Science. 2002, 295 (5559): 1493-1500. 10.1126/science.1069259.

  5. 5.

    Huang AL, Chen X, Hoon MA, Chandrashekar J, Guo W, Trankner D, Ryba NJ, Zuker CS: The cells and logic for mammalian sour taste detection. Nature. 2006, 442 (7105): 934-938. 10.1038/nature05084.

  6. 6.

    LopezJimenez ND, Cavenagh MM, Sainz E, Cruz-Ithier MA, Battey JF, Sullivan SL: Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. J Neurochem. 2006, 98 (1): 68-77. 10.1111/j.1471-4159.2006.03842.x.

  7. 7.

    Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF: A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci. 2002, 5 (11): 1169-1176. 10.1038/nn952.

  8. 8.


  9. 9.

    Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ: Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell. 2003, 112 (3): 293-301. 10.1016/S0092-8674(03)00071-0.

  10. 10.

    Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Perez CA, Shigemura N, Yoshida R, Mosinger B, Glendinning JI, Ninomiya Y, Margolskee RF: Trpm5 null mice respond to bitter, sweet, and umami compounds. Chem Senses. 2006, 31 (3): 253-264. 10.1093/chemse/bjj027.

  11. 11.

    Talavera K, Yasumatsu K, Voets T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B: Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature. 2005, 438 (7070): 1022-1025. 10.1038/nature04248.

  12. 12.

    Liu D, Liman ER: Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc Natl Acad Sci U S A. 2003, 100 (25): 15160-15165. 10.1073/pnas.2334159100.

  13. 13.

    Prawitt D, Monteilh-Zoller MK, Brixel L, Spangenberg C, Zabel B, Fleig A, Penner R: TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i. Proc Natl Acad Sci U S A. 2003, 100 (25): 15166-15171. 10.1073/pnas.2334624100.

  14. 14.

    Hofmann T, Chubanov V, Gudermann T, Montell C: TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel. Curr Biol. 2003, 13 (13): 1153-1158. 10.1016/S0960-9822(03)00431-7.

  15. 15.

    Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP: TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell. 2002, 109 (3): 397-407. 10.1016/S0092-8674(02)00719-5.

  16. 16.

    Teulon J. KYMM: Ca-activated nonselective cation channels. In Pharmacology of ionic channel function: activators and inhibi- tors. 2000, Berlin , Springer-Verlag, 625-649.

  17. 17.


  18. 18.

    Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS: An amino-acid taste receptor. Nature. 2002, 416 (6877): 199-202. 10.1038/nature726.

  19. 19.


  20. 20.

    Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS: A novel family of mammalian taste receptors. Cell. 2000, 100 (6): 693-702. 10.1016/S0092-8674(00)80705-9.

  21. 21.


  22. 22.


  23. 23.

    Hofer D, Puschel B, Drenckhahn D: Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin. Proc Natl Acad Sci U S A. 1996, 93 (13): 6631-6634. 10.1073/pnas.93.13.6631.

  24. 24.

    Hofer D, Drenckhahn D: Identification of the taste cell G-protein, alpha-gustducin, in brush cells of the rat pancreatic duct system. Histochem Cell Biol. 1998, 110 (3): 303-309. 10.1007/s004180050292.

  25. 25.

    Finger TE, Bottger B, Hansen A, Anderson KT, Alimohammadi H, Silver WL: Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc Natl Acad Sci U S A. 2003, 100 (15): 8981-8986. 10.1073/pnas.1531172100.

  26. 26.

    Sbarbati A, Merigo F, Benati D, Tizzano M, Bernardi P, Crescimanno C, Osculati F: Identification and characterization of a specific sensory epithelium in the rat larynx. J Comp Neurol. 2004, 475 (2): 188-201. 10.1002/cne.20172.

  27. 27.

    Sbarbati A, Merigo F, Benati D, Tizzano M, Bernardi P, Osculati F: Laryngeal chemosensory clusters. Chem Senses. 2004, 29 (8): 683-692. 10.1093/chemse/bjh071.

  28. 28.

    Merigo F, Benati D, Tizzano M, Osculati F, Sbarbati A: alpha-Gustducin immunoreactivity in the airways. Cell Tissue Res. 2005, 319 (2): 211-219. 10.1007/s00441-004-1007-2.

  29. 29.

    Rozengurt N, Wu S, Chen MC, Huang C, Sternini C, Rozengurt E: Co-localization of the {alpha} subunit of gustducin with PYY and GLP-1 in L cells of human colon. Am J Physiol Gastrointest Liver Physiol. 2006, 291 (5): G792-G802. 10.1152/ajpgi.00074.2006.

  30. 30.

    Sbarbati A, Osculati F: The taste cell-related diffuse chemosensory system. Prog Neurobiol. 2005, 75 (4): 295-307. 10.1016/j.pneurobio.2005.03.001.

  31. 31.

    Finger TE: Evolution of taste and solitary chemoreceptor cell systems. Brain Behav Evol. 1997, 50 (4): 234-243.

  32. 32.

    Wakisaka S: Lectin histochemistry of taste buds in the circumvallate papilla of the rat. Chem Senses. 2005, 30 Suppl 1: i46-i47. 10.1093/chemse/bjh106.

  33. 33.

    Enklaar T, Esswein M, Oswald M, Hilbert K, Winterpacht A, Higgins M, Zabel B, Prawitt D: 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. 2000, 67 (2): 179-187. 10.1006/geno.2000.6234.

  34. 34.

    Prawitt D, Enklaar T, Klemm G, Gartner B, Spangenberg C, Winterpacht A, Higgins M, Pelletier J, Zabel B: 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. 2000, 9 (2): 203-216. 10.1093/hmg/9.2.203.

  35. 35.

    Rhodin J, Dalhamn T: Electron microscopy of the tracheal ciliated mucosa in rat. Z Zellforsch Mikrosk Anat. 1956, 44 (4): 345-412. 10.1007/BF00345847.

  36. 36.

    Meyrick B, Reid L: The alveolar brush cell in rat lung--a third pneumonocyte. J Ultrastruct Res. 1968, 23 (1): 71-80. 10.1016/S0022-5320(68)80032-2.

  37. 37.

    Lauweryns JM, Cokelaere M: Hypoxia-sensitive neuro-epithelial bodies. Intrapulmonary secretory neuroreceptors, modulated by the CNS. Z Zellforsch Mikrosk Anat. 1973, 145 (4): 521-540. 10.1007/BF00306722.

  38. 38.

    Springall DR, Polak JM: Quantitative microscopical methods for the identification and localisation of nerves and neuroendocrine cell markers in mammalian lung. Microsc Res Tech. 1997, 37 (1): 92-100. 10.1002/(SICI)1097-0029(19970401)37:1<92::AID-JEMT9>3.0.CO;2-Y.

  39. 39.

    Hofer D, Asan E, Drenckhahn D: Chemosensory Perception in the Gut. News Physiol Sci. 1999, 14: 18-23.

  40. 40.

    Sbarbati A, Osculati F: A new fate for old cells: brush cells and related elements. J Anat. 2005, 206 (4): 349-358. 10.1111/j.1469-7580.2005.00403.x.

  41. 41.

    Hofer D, Drenckhahn D: Identification of brush cells in the alimentary and respiratory system by antibodies to villin and fimbrin. Histochemistry. 1992, 98 (4): 237-242. 10.1007/BF00271037.

  42. 42.

    Kasper M, Hofer D, Woodcock-Mitchell J, Migheli A, Attanasio A, Rudolf T, Muller M, Drenckhahn D: Colocalization of cytokeratin 18 and villin in type III alveolar cells (brush cells) of the rat lung. Histochemistry. 1994, 101 (1): 57-62. 10.1007/BF00315832.

  43. 43.

    Luciano L, Reale E, Ruska H: [On a glycogen containing brusc cell in the rectum of the rat]. Z Zellforsch Mikrosk Anat. 1968, 91 (1): 153-158. 10.1007/BF00336990.

  44. 44.

    Voets T, Talavera K, Owsianik G, Nilius B: Sensing with TRP channels. Nat Chem Biol. 2005, 1 (2): 85-92. 10.1038/nchembio0705-85.

  45. 45.

    Montell C: TRP channels in Drosophila photoreceptor cells. J Physiol. 2005, 567 (Pt 1): 45-51. 10.1113/jphysiol.2005.092551.

  46. 46.

    Elsaesser R, Montani G, Tirindelli R, Paysan J: Phosphatidyl-inositide signalling proteins in a novel class of sensory cells in the mammalian olfactory epithelium. Eur J Neurosci. 2005, 21 (10): 2692-2700. 10.1111/j.1460-9568.2005.04108.x.

  47. 47.

    Yoshii K: Gap Junctions among Taste Bud Cells in Mouse Fungiform Papillae. Chem Senses. 2005, 30 Suppl 1: i35-i36. 10.1093/chemse/bjh100.

  48. 48.

    Roper SD: Cell communication in taste buds. Cell Mol Life Sci. 2006

  49. 49.

    Akisaka T, Oda M: Taste buds in the vallate papillae of the rat studied with freeze-fracture preparation. Arch Histol Jpn. 1978, 41 (1): 87-98.

  50. 50.

    Liman ER: Regulation by voltage and adenine nucleotides of a Ca2+-activated cation channel from hamster vomeronasal sensory neurons. J Physiol. 2003, 548 (Pt 3): 777-787. 10.1113/jphysiol.2002.037119.

  51. 51.

    Asan E, Drenckhahn D: Immunocytochemical characterization of two types of microvillar cells in rodent olfactory epithelium. Histochem Cell Biol. 2005, 123 (2): 157-168. 10.1007/s00418-005-0759-4.

  52. 52.

    Hofer D, Shin DW, Drenckhahn D: Identification of cytoskeletal markers for the different microvilli and cell types of the rat vomeronasal sensory epithelium. J Neurocytol. 2000, 29 (3): 147-156. 10.1023/A:1026548020851.

  53. 53.

    Lin W, Margolskee R, Donnert G, Hell SW, Restrepo D: Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals. Proc Natl Acad Sci U S A. 2007, 104 (7): 2471-2476. 10.1073/pnas.0610201104.

  54. 54.

    Lauweryns JM, Cokelaere M, Lerut T, Theunynck P: Cross-circulation studies on the influence of hypoxia and hypoxaemia on neuro-epithelial bodies in young rabbits. Cell Tissue Res. 1978, 193 (3): 373-386. 10.1007/BF00225336.

  55. 55.

    Rozengurt E: Taste Receptors in the Gastrointestinal Tract. I. Bitter taste receptors and {alpha}-gustducin in the mammalian gut. Am J Physiol Gastrointest Liver Physiol. 2006, 291 (2): G171-7. 10.1152/ajpgi.00073.2006.

  56. 56.

    Bezencon C, le Coutre J, Damak S: Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem Senses. 2006

  57. 57.

    Isomaki AM: A new cell type (tuft cell) in the gastrointestinal mucosa of the rat. A transmission and scanning electron microscopic study. Acta Pathol Microbiol Scand [A]. 1973, Suppl 240:1-35.

  58. 58.

    Luciano L, Reale E: Presence of brush cells in the mouse gallbladder. Microsc Res Tech. 1997, 38 (6): 598-608. 10.1002/(SICI)1097-0029(19970915)38:6<598::AID-JEMT4>3.0.CO;2-B.

  59. 59.

    Nabeyama A, Leblond CP: "Caveolated cells" characterized by deep surface invaginations and abundant filaments in mouse gastro-intestinal epithelia. Am J Anat. 1974, 140 (2): 147-165. 10.1002/aja.1001400203.

  60. 60.

    Sato A, Miyoshi S: Fine structure of tuft cells of the main excretory duct epithelium in the rat submandibular gland. Anat Rec. 1997, 248 (3): 325-331. 10.1002/(SICI)1097-0185(199707)248:3<325::AID-AR4>3.0.CO;2-O.

  61. 61.

    Ogata T: Bicarbonate secretion by rat bile duct brush cells indicated by immunohistochemical localization of CFTR, anion exchanger AE2, Na+/HCO3 -cotransporter, carbonic anhydrase II, Na+/H+ exchangers NHE1 and NHE3, H+/K+-ATPase, and Na+/K+-ATPase. Med Mol Morphol. 2006, 39 (1): 44-48. 10.1007/s00795-006-0312-0.

  62. 62.

    Wada R, Watanabe T, Nakagawa K, Higuchi K, Arakawa T, Kuroki T, Kaneda K: Structure of lamina propria lymphoid follicles and associated epithelium in the gastric mucosa during Helicobacter pylori infection in ulcer-bearing Mongolian gerbils. J Submicrosc Cytol Pathol. 2000, 32 (2): 159-167.

  63. 63.

    Hijiya K, Okada Y, Tankawa H: Ultrastructural study of the alveolar brush cell. J Electron Microsc (Tokyo). 1977, 26 (4): 321-329.

  64. 64.

    Hijiya K: Electron microscope study of the alveolar brush cell. J Electron Microsc (Tokyo). 1978, 27 (3): 223-227.

  65. 65.

    Watson JH, Brinkman GL: Electron Microscopy Of The Epithelial Cells Of Normal And Bronchitic Human Bronchus. Am Rev Respir Dis. 1964, 90: 851-866.

  66. 66.

    Gebhard A, Gebert A: Brush cells of the mouse intestine possess a specialized glycocalyx as revealed by quantitative lectin histochemistry. Further evidence for a sensory function. J Histochem Cytochem. 1999, 47 (6): 799-808.

  67. 67.

    Silva DG: The fine structure of multivesicular cells with large microvilli in the epithelium of the mouse colon. J Ultrastruct Res. 1966, 16 (5): 693-705.

  68. 68.

    Luciano L, Reale E, Ruska H: [On a "chemoreceptive" sensory cell in the tachea of the rat]. Z Zellforsch Mikrosk Anat. 1968, 85 (3): 350-375. 10.1007/BF00328847.

  69. 69.

    Luciano L, Reale E: Brush cells of the mouse gallbladder. A correlative light- and electron-microscopical study. Cell Tissue Res. 1990, 262 (2): 339-349. 10.1007/BF00309889.

  70. 70.


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Kaske, S., Krasteva, G., König, P. et al. TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells. BMC Neurosci 8, 49 (2007) doi:10.1186/1471-2202-8-49

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  • Human Embryonic Kidney
  • Olfactory Epithelium
  • Transient Receptor Potential Channel
  • Sensory Epithelium
  • Brush Cell