A balanced intake of macronutrients such as proteins, carbohydrates and fats is essential for the organism, and insufficient protein intake leads to several diseases, including kwashiorkor. Protein-deficient animals have a dietary behavior which is selecting food sources that contain essential amino acids (EAAs) rather than non-essential amino acids. Recently, a neuropeptide called CNMamide (CNMa) was found in Drosophila melanogaster to be highly expressed in enterocytes of the midgut during protein depletion to modulate EAA-specific selective dietary behavior. CNMa expression in these enterocytes is up-regulated in response to protein depletion through the GCN2-ATF4 and TOR-MITF pathways, each of which trigger a compensatory appetite for EAA (Kim, et al. 2021, Nature). Remarkably, flies fed a holidic diet lacking a single L-EAA had enhanced CNMa expression, suggesting the presence of a molecular sensor that recognizes each L-EAA. We have carried out RNAi screening to identify candidate molecules that sense or detect each EAA and are currently characterizing these putative sensors using molecular, genetic and biochemical approaches.
Kim, B., Kanai, M.I., Oh, Y. et al. Response of the microbiome–gut–brain axis in Drosophila to amino acid deficit. Nature593, 570–574 (2021). https://doi.org/10.1038/s41586-021-03522-2