Fig. 4

Simplified Schematic of mTORC1 Regulation. In the post-prandial state an increase in amino acid and insulin availability results in Akt phosphorylation by PDK1 at serine 308, and Redd1/2 and the TSC complex are inhibited. Under these conditions, Rheb is active at the lysosomal membrane and can, in turn, activate mTORC1 kinase activity. With sufficient amino acids in the cell, the Rag heterodimer is recruited to the lysosome where it interacts with Rheb to increase mTORC1 kinase activity. This results in increased protein synthesis and inhibition of autophagy via phosphorylation of S6K1 and 4E-BP1, and ULK1 and TFEB, respectively. In the current study, EAA ingestion in the group that did not receive chloroquine, we found that the following proteins/protein complexes depicted in the schematic had increased mRNA expression (p < 0.05 or p < 0.10): SNAT9, CAT1, LAT2, PAT1, SESTRIN2, REDD1, TSC-TSC2 complex, Ragulator, GATOR1 and GATOR2, PI3K, mTORC1, and TFEB. For a complete listing of the genes and how the conditions of the study changed mRNA expression, refer to Additional file 1: Tables S1 and S2 in the supplement. AA = amino acids, LEU = leucine, ARG = arginine, GLN = glutamine, GAP = GTPase activating protein, GEF = guanine exchange factor, GTP = guanine triphosphate, GDP = guanine diphosphate. H + =hydrogen ion (proton), O2 = oxygen. Text within shapes = protein or subunit names. Dotted lines and arrows indicate repressed functions under the stated conditions