Functional interaction between TAS2R receptors and G-protein alpha subunits expressed in taste receptor cells.

Bitter taste perception is a conserved chemical sense against the ingestion of poisonous substances in mammals. It could be mediated by G protein-coupled receptors that need the appropriate G proteins to transduce the signals. TAS2R receptors and a G protein α subunit, α–gustducin are believed to be key molecules for its perception (Margolskee, 2002; Montmayeur and Matsunami, 2002), but little is known about the molecular basis for its interaction. In the present study, we used a heterologous expression system to determine a specific domain of gustducin necessary to TAS2R coupling. Two chimeric Gα16 proteins harboring 37 and 44 gustducin-specific sequences at their C termini (G16/gust37 and G16/gust44) responded to different TAS2R receptors with known ligands in dose-dependent manner, but G16, G16/gust 23, G16/gust11 and G16/gust5 did not exhibit any responses (Figure 1). The former two chimeras contained a predicted β6 sheet, an α5 helix and an extreme C-terminus of gustducin, and all the domains were indispensable to the expression of TAS2R activity. Taste receptor cells express a variety of Gαi subunit, but these functions are not well known. We next expressed G16 protein chimeras with the corresponding domain from other Gαi proteins, cone-transducin (Gαt2), Gαi2 and Gαz (G16/t2, G16/ i2 and G16/z). As a result, G16/t2 and G16/i2 produced specific responses of TAS2Rs, but G16/z did not (Figure 1). Since Gαt2 and Gαi2 are expressed in taste receptors cells, these may be also involved in bitter taste perception via TAS2R receptors. The present Gα16based chimeras could be powerful tools to analyze the functions of many orphan G protein-coupled taste receptors.