T1R

T1R refers to a small family of class C G protein-coupled receptors that mediate sweet and umami taste. In mammals, T1Rs are encoded by the TAS1R1, TAS1R2, and TAS1R3 genes and are expressed in gustatory taste receptor cells of the tongue and soft palate. They are also found in other tissues such as the gastrointestinal tract and pancreas, where they participate in nutrient sensing and metabolic regulation.

T1Rs have the structural features of class C GPCRs, including a large extracellular Venus flytrap domain that binds ligands, a cysteine-rich domain, and seven transmembrane segments. They function as heterodimers: the T1R2/T1R3 complex forms the canonical sweet receptor, while the T1R1/T1R3 complex forms the umami receptor. Individual subunits require dimerization to form a functional receptor.

Ligands and signaling: The T1R2/T1R3 receptor is activated by a broad range of sweet-tasting compounds, including natural sugars like sucrose and glucose as well as artificial sweeteners. The T1R1/T1R3 receptor responds to L-glutamate and is potentiated by purine nucleotides such as inosine monophosphate (IMP) and guanosine monophosphate (GMP), contributing to umami perception. Activation initiates a G protein–coupled signaling cascade involving gustducin and phospholipase Cβ2, leading to increases in intracellular calcium and neurotransmitter release to afferent gustatory neurons.

Genetic and physiological relevance: Variations in TAS1R genes influence individual taste sensitivity to sweet and umami stimuli. Beyond taste, T1Rs in the gut and other tissues contribute to post-ingestive nutrient sensing and metabolic regulation, highlighting roles that extend beyond the oral cavity.