Nelson Greg, Chandrashekar Jayaram, Hoon Mark A, Feng Luxin, Zhao Grace, Ryba Nicholas J P, Zuker Charles S
Howard Hughes Medical Institute and Departments of Biology and Neurosciences, University of California at San Diego, La Jolla, California, 92093-0649, USA.
Nature. 2002 Mar 14;416(6877):199-202. doi: 10.1038/nature726. Epub 2002 Feb 24.
The sense of taste provides animals with valuable information about the nature and quality of food. Mammals can recognize and respond to a diverse repertoire of chemical entities, including sugars, salts, acids and a wide range of toxic substances. Several amino acids taste sweet or delicious (umami) to humans, and are attractive to rodents and other animals. This is noteworthy because L-amino acids function as the building blocks of proteins, as biosynthetic precursors of many biologically relevant small molecules, and as metabolic fuel. Thus, having a taste pathway dedicated to their detection probably had significant evolutionary implications. Here we identify and characterize a mammalian amino-acid taste receptor. This receptor, T1R1+3, is a heteromer of the taste-specific T1R1 and T1R3 G-protein-coupled receptors. We demonstrate that T1R1 and T1R3 combine to function as a broadly tuned L-amino-acid sensor responding to most of the 20 standard amino acids, but not to their D-enantiomers or other compounds. We also show that sequence differences in T1R receptors within and between species (human and mouse) can significantly influence the selectivity and specificity of taste responses.
味觉为动物提供有关食物性质和质量的宝贵信息。哺乳动物能够识别并对多种化学物质作出反应，包括糖类、盐类、酸类以及多种有毒物质。几种氨基酸对人类来说尝起来是甜的或美味的（鲜味），并且对啮齿动物和其他动物具有吸引力。这一点值得注意，因为L-氨基酸作为蛋白质的组成部分、许多具有生物学意义的小分子的生物合成前体以及代谢燃料发挥作用。因此，拥有一条专门用于检测它们的味觉通路可能具有重大的进化意义。在这里，我们鉴定并表征了一种哺乳动物氨基酸味觉受体。这种受体T1R1+3是味觉特异性T1R1和T1R3 G蛋白偶联受体的异源二聚体。我们证明，T1R1和T1R3结合起来作为一种广泛调谐的L-氨基酸传感器，对20种标准氨基酸中的大多数作出反应，但对它们的D-对映体或其他化合物没有反应。我们还表明，物种内部（人和小鼠）以及物种之间T1R受体的序列差异会显著影响味觉反应的选择性和特异性。
