Fig. 3

Regulation of mTORC1 by amino acids. a The Rags are found in their inactive state under low amino acid conditions and therefore are unable to recruit mTORC1 to the lysosomal membrane for activation by Rheb-GTP. Ragulator and v-ATPase are in their inactive state, whereas GATOR1 exerts GAP-activity towards RagA/B, ensuring an inactive state of these Rags. b An increase in the amino acid concentration triggers a conformational change in v-ATPase and Ragulator, which initiates GEF activity towards RagA/B of the latter. FLCN and its binding partners exhibit GAP activity towards RagC/D and thereby activating them as well. Additionally, GATOR1 its GAP activity is inhibited due to inhibition of GATOR2. These actions lead to the active heterodimer of GTP-bound RagA/B and GDP-bound RagC/D, which then recruit mTORC1 to the lysosomal surface where it can be activated by Rheb-GTP. Figure based on [99]