1. Human genetic polymorphisms in T1R1 and T1R3 taste receptor subunits affect their function
- Author
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Claire Schlegel-Le-Poupon, Annick Faurion, Jean-Claude Pernollet, Singh Preet Bano, Christine Belloir, Hélène Débat, Loïc Briand, Brice Hoffmann, Anna Wiencis, Maud Sigoillot, Claude Nespoulous, Marta Grauso, Jean-Pierre Montmayeur, Mariam Raliou, Didier Trotier, Briand, Loïc, Neurobiologie de l'Olfaction et de la Prise Alimentaire - Biochimie de l'Olfaction et de la Gustation, Institut National de la Recherche Agronomique (INRA), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut de Neurobiologie Alfred Fessard (INAF), Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique ( INRA ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Université Versailles St-Quentin, Institut de Neurobiologie Alfred Fessard ( INAF ), Centre National de la Recherche Scientifique ( CNRS ), and Neurobiologie de l'Olfaction et de la Prise Alimentaire (NOPA)
- Subjects
Nonsynonymous substitution ,Models, Molecular ,Taste ,030309 nutrition & dietetics ,Physiology ,Monosodium glutamate ,MESH : Polymorphism, Genetic ,saccharin ,MESH : Immunohistochemistry ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,récepteur gustatif ,goût ,Umami ,MESH : Blotting, Western ,MESH: Receptors, G-Protein-Coupled ,perception ,gustation ,Receptors, G-Protein-Coupled ,Behavioral Neuroscience ,chemistry.chemical_compound ,MESH : Taste Threshold ,Taste receptor ,taste receptor ,Sodium Glutamate ,structure cristalline ,dynamique moléculaire ,[ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics ,papillae ,Cells, Cultured ,Genetics ,0303 health sciences ,molecular dynamic ,MESH: Taste Threshold ,mammifère ,récepteur couplé aux protéines G ,MESH: Amino Acid Substitution ,umami ,Immunohistochemistry ,Sensory Systems ,Transmembrane domain ,Biochemistry ,[ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Alimentation et Nutrition ,Taste Threshold ,récepteur glutamate ,MESH : Receptors, G-Protein-Coupled ,MESH: Models, Molecular ,MESH: Cells, Cultured ,t1r3 ,crystal structure ,t1r1 ,MESH : Sodium Glutamate ,MESH : Models, Molecular ,Blotting, Western ,différence individuelle ,G protein coupled receptor ,glutamate ,individual difference ,mammalian sweet ,03 medical and health sciences ,protein coupled receptor ,MESH : Amino Acid Substitution ,man ,Physiology (medical) ,MESH : Cells, Cultured ,MESH: Polymorphism, Genetic ,saccharine ,MESH: Blotting, Western ,Food and Nutrition ,Humans ,mammals ,l glutamate ,human ,metabotropic glutamate receptor ,umami taste ,030304 developmental biology ,G protein-coupled receptor ,MESH: Humans ,Polymorphism, Genetic ,papilla ,MESH: Sodium Glutamate ,MESH : Humans ,snp ,MESH: Immunohistochemistry ,gustatory receptor ,molecular dynamics ,chemistry ,crystalline structure ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Amino Acid Substitution ,Metabotropic glutamate receptor ,msg ,saccharin preference ,humain ,papille - Abstract
International audience; Umami is the typical taste induced by monosodium glutamate (MSG), which is thought to be detected by the heterodimeric G protein-coupled receptor, T1R1 and T1R3. Previously, we showed that MSG detection thresholds differ substantially between individuals and we further showed that nontaster and hypotaster subjects are associated with nonsynonymous single polymorphisms occurring in the T1R1 and T1R3 genes. Here, we show using functional expression that both amino acid substitutions (A110V and R507Q) in the N-terminal ligand-binding domain of T1R1 and the 2 other ones (F749S and R757C), located in the transmembrane domain of T1R3, severely impair in vitro T1R1/T1R3 response to MSG. A molecular model of the ligand-binding region of T1R1/T1R3 provides a mechanistic explanation supporting functional expression data. The data presented here support causal relations between the genotype and previous in vivo psychophysical studies in human evaluating sensitivity to MSG.
- Published
- 2011
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