1. Howard Hughes Medical Institute and Departments of Biology and Neurosciences, University of California at San Diego, La Jolla, California, 92093-0649, USA
2. National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA

Correspondence to: Charles S. Zuker¹ Correspondence and requests for materials should be addressed to C.S.Z. (e-mail: Email: charles@flyeye.ucsd.edu).

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 substances¹. Several amino acids taste sweet or delicious (umami) to humans, and are attractive to rodents and other animals². 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.