Allosteric modulation of the fish taste receptor type 1 (T1R) family by the extracellular chloride ion.

Many G protein-coupled receptors (GPCRs) are allosterically modulated by inorganic ions. Although the intraoral ionic composition of the oral cavity varies depending on the living environment and feeding behavior, little is known about whether and how it affects the function of taste receptor type 1 (T1R), a member of the class C GPCR family. Here, we report that chloride ions allosterically modulate the functions of specific fish T1Rs, namely, mfT1R2a/mfT1R3 and zfT1R2a/zfT1R3. Site-directed mutagenesis revealed mfT1R2a K265, which lies in the extracellular domain of mfT1R2a, to be as a critical residue for the modulation of mfT1R2a/mfT1R3 by Cl−. However, this residue is not conserved in zfT1R2a, and the introduction of the key residue at the corresponding site of another T1R, mfT1R2b, did not confer Cl− susceptibility. These results indicate the variability of the determinants of Cl− susceptibility. [ABSTRACT FROM AUTHOR]