The secretion-based signaling between the Drosophila fat body and IPCs upon sensing the level of circulating amino acids. Top: When amino acids are available, they are transported into the fat body cells by Slimfast, where they activate mTORC1 (see mTORC1 activation text box). The nutrient responsive coactivator PGC-1 stimulates stunted expression, giving rise to the SunA and SunB peptides that are secreted into the hemolymph. SunA and SunB subsequently bind to their receptor Methuselah on the plasma membrane of IPCs in the brain. The IPCs transcribe the Dilp genes, leading to the accumulation of Dilps 3, 2, and 5. Activation of Methuselah triggers intracellular calcium release, which stimulates Dilps secretion to the hemolymph. In turn, Dilps activate the InR in the fat body, which increases mTORC1 activity further via the insulin-Akt pathway (see mTORC1 activation text box). Bottom: Upon amino-acid starvation, mTORC1 activation is reduced, leading to a reduction of SunA and SunB. It is also possible that their secretion is inhibited through the increase of the ERK7 level. Decreased SunA and SunB secretion leads to a decreased stimulation of Methuselah, resulting in a reduced Dilp secretion from IPCs where they accumulate. ERK7 level in the IPCs is increased, possibly contributing to secretion inhibition. Reduced Dilp secretion during amino-acid starvation effectively reduces mTORC1 activation and overall growth.