Amino acids activate parallel chemosensory pathways in Drosophila.

Amino acids (AAs) are essential dietary macronutrients that impact an organism's fitness in a concentration-dependent manner, but the mechanisms mediating AA detection to drive consumption are less clear. In Drosophila, we identified the repertoire of taste cells and receptors that are salient for feeding initiation when flies encounter a glutamate-rich AA peptide mixture, tryptone, using in vivo calcium imaging and the proboscis extension response (PER). We found that tryptone attraction occurs through sweet cells, whereas feeding aversion is mediated through Ionotropic Receptor 94e (IR94e) cells and bitter cells, dependent on concentration. Further, our results corroborate previous findings that IR76b, IR51b, and IR94e detect AAs in specific cell types, even when exposed to a more complex peptide mixture. Additionally, we describe a new role for the appetitive IR56d receptor and bitter Gustatory Receptors (GRs) in sensing tryptone. This work establishes a cellular and molecular framework salient for AA and peptide feeding initiation and highlights redundancy in aversive pathways that regulate AA feeding.