The G protein-coupled receptor GPRC5C is a saccharide sensor with a novel 'off' response

GPRC5C is an orphan G protein-coupled receptor (GPCR) that belongs to the class C GPCR family. Although GPRC5C is expressed in various organs, its function and ligand are still undetermined. We found that GPRC5C is expressed in mouse taste cells, enterocytes, and pancreatic & alpha;-cells. In functional imaging assays, HEK293 cells heterologously expressing GPRC5C and the chimeric G protein & alpha; subunit G & alpha;16-gust44 showed robust intracellular Ca2+ increases in response to monosaccharides, disaccharides, and a sugar alcohol, but not an artificial sweetener or sweet-tasting amino acid. Notably, Ca2+ increases occurred after washout, not during stimulation. Our findings suggest that GPRC5C has receptor properties which lead to novel 'off' responses to saccharide detachment and may work as an internal or external chemosensor specifically tuned to natural sugars.

Automated summary

GPRC5C is an orphan GPCR expressed in various organs, but its function and ligand remain unknown. In this study, GPRC5C was found to be expressed in mouse taste cells, enterocytes, and pancreatic α-cells. Functional imaging assays showed that HEK293 cells expressing GPRC5C and a chimeric G protein α subunit, Gα16-gust44, responded to monosaccharides, disaccharides, and a sugar alcohol with robust intracellular Ca2+ increases. These responses were not observed with artificial sweeteners or sweet-tasting amino acids. The findings suggest that GPRC5C acts as a chemosensor specifically tuned to natural sugars, exhibiting novel "off" responses to saccharide detachment.