Sci. STKE, 5 October 2004
TASTE Two Ways to Be Sweet
The T1R family of G protein-coupled receptors (GPCRs), which are expressed in taste buds, detect sweet and umami tastes. Coexpressed T1R1 and T1R3 respond to the umami taste of glutamate, whereas coexpressed T1R2 and T1R3 respond to numerous sweet substances, including sugars, amino acids, proteins, and synthetic sweeteners. In humans, aspartame, neotame, and cyclamate stimulate T1R2-T1R3, whereas rat T1R2-T1R3 does not respond to these sweeteners. Xu et al. constructed rat-human chimeric T1R2 and T1R3 proteins in which the N-terminal region (containing the large extracellular "Venus flytrap" domain) from one species was fused to the C-terminal region (containing the transmembrane and intracellular domains) of the other. Analysis of various chimeric and human or rat wild-type GPCR combinations expressed in HEK-293 cells implicated the T1R2 N-terminal region in sensing aspartame and neotame, whereas extracellular portions of the C-terminal region of T1R3 were implicated in sensing cyclamate and in sensitivity to lactisole, a human-specific sweet taste inhibitor. Lactisole inhibited the response to glutamate (and glutamate plus the umami taste enhancer 5'-inosine monophosphate) both in vitro and in human taste tests, whereas cyclamate (whose sweetness would have overwhelmed an umami taste test) enhanced the T1R2-T1R3 response in vitro. Thus, the authors conclude that both T1R2 and T1R3 are required for a functional sweet taste receptor and that the structural diversity of sweeteners may depend in part on the existence of distinct ligand-binding sites.
H. Xu, L. Staszewski, H. Tang, E. Adler, M. Zoller, X. Li, Different functional roles of T1R subunits in the heteromeric taste receptors. Proc. Natl. Acad. Sci. U.S.A. 101, 14258-14263 (2004). [Abstract] [Full Text]
Citation: Two Ways to Be Sweet. Sci. STKE 2004, tw355 (2004).
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