Taste receptor type 1 member 2 and Taste receptor type 1 member 3 heterodimer (Sweet taste receptor) (TAS1R2/TAS1R3)

The sweet taste receptor is a heterodimeric Class C G protein-coupled receptor (GPCR) composed of the Taste receptor type 1 member 2 (TAS1R2) and Taste receptor type 1 member 3 (TAS1R3) subunits [4, 6, 12]. Primarily localized in the taste buds of the tongue, it functions as the principal sensor for sweet-tasting substances, including caloric sugars, high-potency artificial sweeteners, and certain sweet proteins [1, 8, 13]. Beyond the oral cavity, the receptor is expressed in extra-oral tissues such as the gastrointestinal tract, pancreas, and brain, where it plays a critical role in nutrient sensing and energy homeostasis [3, 6, 10]. In the gut, activation of these receptors by sugars or sweeteners triggers the release of metabolic hormones like glucagon-like peptide-1 (GLP-1), which modulates insulin secretion and glucose absorption [10, 11, 15]. Because of its central role in dietary choice and metabolic signaling, the receptor is a major target for both the food industry and pharmaceutical research focused on obesity and type 2 diabetes [6, 9, 12]. Interactions with various ligands, ranging from natural sweeteners to pharmacological inhibitors like lactisole, highlight its potential for therapeutic modulation and the complexity of its long-term impact on metabolic health [11, 15, 17].

Other names

TAS1R2TAS1R3T1R2T1R3GPR70GPR71Sweet taste receptorSTRTaste receptor type 1 member 2Taste receptor type 1 member 3

Binding of a sweet ligand to the extracellular Venus Flytrap domains of the TAS1R2/TAS1R3 heterodimer induces a conformational change that activates the heterotrimeric G-protein gustducin [1, 12, 13]. This triggers a signaling cascade involving the activation of phospholipase C beta 2 (PLCβ2), leading to the generation of inositol trisphosphate (IP3) and subsequent release of intracellular calcium [4, 10, 11]. The elevation of calcium levels opens the transient receptor potential cation channel M5 (TRPM5), causing cell depolarization and the release of ATP as a neurotransmitter to signal sweetness to the brain or trigger hormonal responses in extra-oral tissues [3, 7, 8].