Human genetic polymorphisms in T1R1 and T1R3 taste receptor subunits affect their function.
Résumé
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.
Mots clés
papilla
gustatory receptor
msg
snp
taste receptor
papillae
molecular dynamics
t1r3
mammals
t1r1
crystal structure
mammalian sweet
molecular dynamic
saccharin preference
individual difference
umami taste
protein coupled receptor
metabotropic glutamate receptor
crystalline structure
saccharin
G protein coupled receptor
gustation
man
human
l glutamate
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