The expression of canonical chemosensory receptors, such as the sweet taste receptor (TAS1R2/TAS1R3), has been demonstrated in a variety of extra-oral cells and tissues. Gene expression studies have revealed transcripts of all three TAS1R subunits, and all 25 bitter taste receptor (TAS2R) genes, as well as of some of the eight human metabotropic glutamate receptors (GRMs), in different types of immune cells, where they are involved, for example, in the chemotaxis of human neutrophils and the protection of T-cells from activation-induced cell death. TAS1Rs and GRMs both belong to the class C GPCRs whose characteristic structures are the large extracellular N-terminal and cysteine-rich domains. These distinctive components enable the assembly into constitutive dimeric complexes to accomplish their diverse functions.
Here we show that GRM2 and TAS1R3 co-localize and heterodimerize in human blood leukocytes, by means of immunocytochemistry and co-IP/Western analysis. We validated a hetero­dimerization of recombinant GRM2/TAS1R3 in heterologous test cells by means of BRET, and a gain-of-function luminescence assay with physiological concentrations of monosodium glutamate.
Our results demonstrate a heterodimerization across different families of class C GPCRs in leukocytes, suggesting previously unnoticed, new cellular function-tailored chemoreceptor combinations, enabling our immune system to cope with a vast variety of stimuli.