title: Human genetic polymorphisms in T1R1 and T1R3 taste receptor subunits affect their function.
abstract: 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.
authors.affiliation: Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1197 Neurobiologie de l’Olfaction et de la Prise Alimentaire—Biochimie de l’Olfaction et de la Gustation, Domaine de Vilvert, F-78350, Jouy-en-Josas, France.
authors.forename: Mariam
authors.initials: M
authors.lastname: Raliou
authors.forename: Marta
authors.initials: M
authors.lastname: Grauso
authors.forename: Brice
authors.initials: B
authors.lastname: Hoffmann
authors.forename: Claire
authors.initials: C
authors.lastname: Schlegel-Le-Poupon
authors.forename: Claude
authors.initials: C
authors.lastname: Nespoulous
authors.forename: Hélène
authors.initials: H
authors.lastname: Débat
authors.forename: Christine
authors.initials: C
authors.lastname: Belloir
authors.forename: Anna
authors.initials: A
authors.lastname: Wiencis
authors.forename: Maud
authors.initials: M
authors.lastname: Sigoillot
authors.forename: Singh Preet
authors.initials: SP
authors.lastname: Bano
authors.forename: Didier
authors.initials: D
authors.lastname: Trotier
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Pernollet
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Montmayeur
authors.forename: Annick
authors.initials: A
authors.lastname: Faurion
authors.forename: Loïc
authors.initials: L
authors.lastname: Briand
mesh_terms: D019943:Amino Acid Substitution; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D008958:Models, Molecular; D011110:Polymorphism, Genetic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D012970:Sodium Glutamate / Q000378:metabolism; D013652:Taste Threshold / Q000235:genetics*
chemical_list: D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D012970:Sodium Glutamate