Tas1R1–Tas1R3 taste receptor variants in human fungiform papillae

Monosodium glutamate as well as metabotropic and ionotropic glutamate receptor agonists have been reported to be perceived as umami by humans. In spite of the fact that Tas1R1–Tas1R3 has been shown to mediate most of the glutamate taste sensation in mice other candidate receptors have been put forward for which a clear role in detection is still lacking. This work was aimed at investigating the molecular determinants underlying umami taste detection in humans. First, we show evidence supporting expression of Tas1R1 and Tas1R3 but not mGluRs in the fungiform papillae of several individuals. Next, we report a number of naturally occurring l-glutamate taste receptor variants and their frequency in a population of Caucasian subjects. Detailed analysis of 9 non-synonymous single nucleotide polymorphisms from three l-glutamate taste GPCR candidates uncovers receptor specific clusters such that all substitutions in Tas1R1 are located in the extracellular N-terminal ligand-binding domain while in Tas1R3 they mostly affect residues in the seven transmembrane-spanning core domain responsible for the interaction with antagonists and allosteric modulators. In mGluR1, nsSNPs identified are clustered in the intracellular C-terminal tail, which is thought to play a role in signaling. Taken together, these results suggest that Tas1R1–Tas1R3 receptor variants found in human fungiform papillae might contribute to inter-individual differences of sensitivity to l-glutamate.