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Originally published in Science Express on 17 July 2003
Science 8 August 2003:
Vol. 301. no. 5634, pp. 850 - 853
DOI: 10.1126/science.1087155

Reports

Detection of Sweet and Umami Taste in the Absence of Taste Receptor T1r3

Sami Damak,1* Minqing Rong,1,2* Keiko Yasumatsu,3 Zaza Kokrashvili,1 Vijaya Varadarajan,1 Shiying Zou,1 Peihua Jiang,1 Yuzo Ninomiya,3 Robert F. Margolskee1,2{dagger}

The tastes of sugars (sweet) and glutamate (umami) are thought to be detected by T1r receptors expressed in taste cells. Molecular genetics and heterologous expression implicate T1r2 plus T1r3 as a sweet-responsive receptor,and T1r1 plus T1r3,as well as a truncated form of the type 4 metabotropic glutamate receptor (taste-mGluR4),as umami-responsive receptors. Here,we show that mice lacking T1r3 showed no preference for artificial sweeteners and had diminished but not abolished behavioral and nerve responses to sugars and umami compounds. These results indicate that T1r3-independent sweet- and umami-responsive receptors and/or pathways exist in taste cells.

1 Department of Biophysics and Physiology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, NY 10029, USA.
2 Howard Hughes Medical Institute, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, NY 10029, USA.
3 Section of Oral Neuroscience, Kyushu University 3-1-1, Maidashi, Higashi-ku, Fukuoka 812–8582, Japan.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: bob{at}inka.mssm.edu

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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R. Yoshida, N. Shigemura, K. Sanematsu, K. Yasumatsu, S. Ishizuka, and Y. Ninomiya (2006)
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   Abstract »    Full Text »    PDF »
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K.-i. Nakajima, T. Asakura, J.-i. Maruyama, Y. Morita, H. Oike, A. Shimizu-Ibuka, T. Misaka, H. Sorimachi, S. Arai, K. Kitamoto, et al. (2006)
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   Abstract »    Full Text »    PDF »
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E.R. Delay, N.P. Hernandez, K. Bromley, and R.F. Margolskee (2006)
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   Abstract »    Full Text »    PDF »
The Liaison of Sweet and Savory.
V. Galindo-Cuspinera and P. A.S. Breslin (2006)
Chem Senses 31, 221-225
   Abstract »    Full Text »    PDF »
Trpm5 Null Mice Respond to Bitter, Sweet, and Umami Compounds.
S. Damak, M. Rong, K. Yasumatsu, Z. Kokrashvili, C. A. Perez, N. Shigemura, R. Yoshida, B. Mosinger Jr., J. I. Glendinning, Y. Ninomiya, et al. (2006)
Chem Senses 31, 253-264
   Abstract »    Full Text »    PDF »
Umami responses in mouse taste cells indicate more than one receptor..
Y. Maruyama, E. Pereira, R. F. Margolskee, N. Chaudhari, and S. D. Roper (2006)
J. Neurosci. 26, 2227-2234
   Abstract »    Full Text »    PDF »
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P. Jiang, M. Cui, B. Zhao, L. A. Snyder, L. M. J. Benard, R. Osman, M. Max, and R. F. Margolskee (2005)
J. Biol. Chem. 280, 34296-34305
   Abstract »    Full Text »    PDF »
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N. Wettschureck and S. Offermanns (2005)
Physiol Rev 85, 1159-1204
   Abstract »    Full Text »    PDF »
Structure-Sweetness Relationship in Egg White Lysozyme: Role of Lysine and Arginine Residues on the Elicitation of Lysozyme Sweetness.
T. Masuda, N. Ide, and N. Kitabatake (2005)
Chem Senses 30, 667-681
   Abstract »    Full Text »    PDF »
The representation of taste quality in the Mammalian nervous system..
A. C. Spector and S. P. Travers (2005)
Behav Cogn Neurosci Rev 4, 143-191
   Abstract »    PDF »
Initial Licking Responses of Mice to Sweeteners: Effects of Tas1r3 Polymorphisms.
J. I. Glendinning, S. Chyou, I. Lin, M. Onishi, P. Patel, and K. H. Zheng (2005)
Chem Senses 30, 601-614
   Abstract »    Full Text »    PDF »
Mouse Strain Differences in Gurmarin-sensitivity of Sweet Taste Responses Are Not Associated with Polymorphisms of the Sweet Receptor Gene, Tas1r3.
K. Sanematsu, K. Yasumatsu, R. Yoshida, N. Shigemura, and Y. Ninomiya (2005)
Chem Senses 30, 491-496
   Abstract »    Full Text »    PDF »
Sensory Systems: Taste Perception.
R. F. Margolskee (2005)
Sci. STKE 2005, tr20
   Abstract »    Full Text »    PDF »
Lactisole Interacts with the Transmembrane Domains of Human T1R3 to Inhibit Sweet Taste.
P. Jiang, M. Cui, B. Zhao, Z. Liu, L. A. Snyder, L. M. J. Benard, R. Osman, R. F. Margolskee, and M. Max (2005)
J. Biol. Chem. 280, 15238-15246
   Abstract »    Full Text »    PDF »
Regional Expression Patterns of T1r Family in the Mouse Tongue.
Y. Kusakabe, M.-R. Kim, H. Miura, Y. Shindo, Y. Ninomiya, and A. Hino (2005)
Chem Senses 30, i23-i24
   Full Text »    PDF »
Cloning and Characterization of a Novel mGluR1 Variant from Vallate Papillae that Functions as a Receptor for L-glutamate Stimuli.
A. San Gabriel, H. Uneyama, S. Yoshie, and K. Torii (2005)
Chem Senses 30, i25-i26
   Full Text »    PDF »
Multiple Pathways for Signaling Glutamate Taste in Rodents.
N. Chaudhari, Y. Maruyama, S. Roper, and K. Trubey (2005)
Chem Senses 30, i29-i30
   Full Text »    PDF »
Downstream Signaling Effectors for Umami Taste.
S. C. Kinnamon, W. Lin, T. Ogura, C. Ruiz, and E. Delay (2005)
Chem Senses 30, i31-i32
   Full Text »    PDF »
Signal Transduction of Umami Taste: Insights from Knockout Mice.
M. Rong, W. He, K. Yasumatsu, Z. Kokrashvili, C. A. Perez, B. Mosinger, Y. Ninomiya, R. F. Margolskee, and S. Damak (2005)
Chem Senses 30, i33-i34
   Full Text »    PDF »
Bitter Taste Receptors for Saccharin and Acesulfame K.
C. Kuhn, B. Bufe, M. Winnig, T. Hofmann, O. Frank, M. Behrens, T. Lewtschenko, J. P. Slack, C. D. Ward, and W. Meyerhof (2004)
J. Neurosci. 24, 10260-10265
   Abstract »    Full Text »    PDF »
Gustatory Neural Responses to Umami Taste Stimuli in C57BL/6ByJ and 129P3/J Mice.
M. Inoue, G. K. Beauchamp, and A. A. Bachmanov (2004)
Chem Senses 29, 789-795
   Abstract »    Full Text »    PDF »
Behavioral Comparisons of the Tastes of L-Alanine and Monosodium Glutamate in Rats.
C. C. Taylor-Burds, A. M. Westburg, T. C. Wifall, and E. R. Delay (2004)
Chem Senses 29, 807-814
   Abstract »    Full Text »    PDF »
The Cysteine-rich Region of T1R3 Determines Responses to Intensely Sweet Proteins.
P. Jiang, Q. Ji, Z. Liu, L. A. Snyder, L. M. J. Benard, R. F. Margolskee, and M. Max (2004)
J. Biol. Chem. 279, 45068-45075
   Abstract »    Full Text »    PDF »
Divergence of T2R chemosensory receptor families in humans, bonobos, and chimpanzees.
C. M. Parry, A. Erkner, and J. le Coutre (2004)
PNAS 101, 14830-14834
   Abstract »    Full Text »    PDF »
Monosodium Glutamate and Sweet Taste: Discrimination between the Tastes of Sweet Stimuli and Glutamate in Rats.
B. R. Heyer, C. C. Taylor-Burds, J. D. Mitzelfelt, and E. R. Delay (2004)
Chem Senses 29, 721-729
   Abstract »    Full Text »    PDF »
From the Cover: Different functional roles of T1R subunits in the heteromeric taste receptors.
H. Xu, L. Staszewski, H. Tang, E. Adler, M. Zoller, and X. Li (2004)
PNAS 101, 14258-14263
   Abstract »    Full Text »    PDF »
Stimulus Processing of Glycine is Dissociable from that of Sucrose and Glucose Based on Behaviorally Measured Taste Signal Detection in Sac 'Taster' and 'Non-taster' Mice.
S. Eylam and A. C. Spector (2004)
Chem Senses 29, 639-649
   Abstract »    Full Text »    PDF »
Umami Taste Responses Are Mediated by {alpha}-Transducin and {alpha}-Gustducin.
W. He, K. Yasumatsu, V. Varadarajan, A. Yamada, J. Lem, Y. Ninomiya, R. F. Margolskee, and S. Damak (2004)
J. Neurosci. 24, 7674-7680
   Abstract »    Full Text »    PDF »
Alcohol Activates a Sucrose-Responsive Gustatory Neural Pathway.
C. H. Lemon, S. M. Brasser, and D. V. Smith (2004)
J Neurophysiol 92, 536-544
   Abstract »    Full Text »    PDF »
Responses of the Rat Chorda Tympani Nerve to Glutamate-Sucrose Mixtures.
B.K. Formaker, J.R. Stapleton, S.D. Roper, and M.E. Frank (2004)
Chem Senses 29, 473-482
   Abstract »    Full Text »    PDF »
The Relative Affective Potency of Glycine, L-Serine and Sucrose as Assessed by a Brief-access Taste Test in Inbred Strains of Mice.
C. D. Dotson and A. C. Spector (2004)
Chem Senses 29, 489-498
   Abstract »    Full Text »    PDF »
Oral Zinc Sulfate Solutions Inhibit Sweet Taste Perception.
R. S.J. Keast, T. M. Canty, and P. A.S. Breslin (2004)
Chem Senses 29, 513-521
   Abstract »    Full Text »    PDF »
Genetics of Human Taste Perception.
U.-K. Kim, P.A.S. Breslin, D. Reed, and D. Drayna (2004)
Journal of Dental Research 83, 448-453
   Abstract »    Full Text »    PDF »
Glutamate Taste: Discrimination between the Tastes of Glutamate Agonists and Monosodium Glutamate in Rats.
E.R. Delay, G.M. Sewczak, J.R. Stapleton, and S.D. Roper (2004)
Chem Senses 29, 291-299
   Abstract »    Full Text »    PDF »
Allelic Variation of the Tas1r3 Taste Receptor Gene Selectively Affects Behavioral and Neural Taste Responses to Sweeteners in the F2 Hybrids between C57BL/6ByJ and 129P3/J Mice.
M. Inoue, D. R. Reed, X. Li, M. G. Tordoff, G. K. Beauchamp, and A. A. Bachmanov (2004)
J. Neurosci. 24, 2296-2303
   Abstract »    Full Text »    PDF »
Polymorphisms in the Taste Receptor Gene (Tas1r3) Region Are Associated with Saccharin Preference in 30 Mouse Strains.
D. R. Reed, S. Li, X. Li, L. Huang, M. G. Tordoff, R. Starling-Roney, K. Taniguchi, D. B. West, J. D. Ohmen, G. K. Beauchamp, et al. (2004)
J. Neurosci. 24, 938-946
   Abstract »    Full Text »    PDF »



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