Taste receptor type 1 member 3 homodimer (TAS1R3)

The Taste receptor type 1 member 3 (TAS1R3) homodimer is a Class C G protein-coupled receptor that functions as a low-affinity sensor for high concentrations of natural sugars like sucrose and glucose (Nelson et al., 2001, Cell). While TAS1R3 is widely recognized for its role in heterodimeric complexes that detect sweet (TAS1R2/TAS1R3) and umami (TAS1R1/TAS1R3) tastes, the homodimeric form is specifically responsible for sensing carbohydrates at millimolar levels (Zhao et al., 2003, Cell). This receptor is expressed in both oral taste cells and extra-oral tissues, including the small intestine, pancreas, and hypothalamus, where it plays a vital role in nutrient sensing and metabolic homeostasis (Margolskee et al., 2007, PNAS). In the gut, activation of the TAS1R3 homodimer facilitates the secretion of incretin hormones such as glucagon-like peptide-1 (GLP-1) and regulates the expression of glucose transporters (Mace et al., 2007, Journal of Physiology). Because of its involvement in glucose absorption and insulin secretion, the TAS1R3 homodimer is a target of interest for the treatment of metabolic disorders like type 2 diabetes and obesity (Laffitte et al., 2014, JCI). Pharmacological modulation of this receptor, such as inhibition by the negative allosteric modulator lactisole, offers a pathway to influence sugar-induced metabolic responses (Jiang et al., 2005, JBC).

Other names

T1R3 homodimerTaste receptor type 1 member 3G-protein coupled receptor 70GPR70Sweet taste receptor subunit 3SAC locus

The TAS1R3 homodimer functions as a low-affinity glucose sensor; agonist binding to the extracellular Venus Flytrap domain triggers a conformational change that activates heterotrimeric G-proteins (such as gustducin or Gq/11), leading to phospholipase C beta-2 activation and increased intracellular calcium, which modulates the release of metabolic hormones like GLP-1 (PubMed: 17724332, 12620233).