1. Toward a Molecular Definition of Leucine-Dependent mTORC1 Activation
Robert T. Abraham 
Cell Metabolism 
Volume 23, Issue 3, Pages (March 2016)
DOI: /j.cmet
Copyright © 2016 Elsevier Inc. Terms and Conditions

2. Figure 1 Amino-Acid-Dependent Signaling to mTORC1
During amino acid starvation, Sestrin2 binds to and inhibits GATOR2. GATOR1 exerts a dominant GAP activity on RAG-A/B, rendering the RAG heterodimer inactive (RAGinact), thereby preventing the localization of mTORC1 to the lysosome and the interaction of mTORC1 with activated Rheb (Rheb·GTP). Arginine (Arg) insufficiency in the lysosomal lumen suppresses the transmission of SLC38A9-dependent activating signals through the Ragulator-RAG supercomplex to mTORC1. In amino-acid-replete conditions, Sestrin2 binds to free leucine (Leu), which blocks the Sestrin2-GATOR2 interaction and allows GATOR2 to overcome the GAP activity of GATOR1, favoring the activation of the RAG heterodimer (RAGact). Concomitant export of Arg from the lysosomal lumen via SLC38A9 further stimulates the accumulation of RAGact. mTORC1 is recruited to the lysosomal membrane, juxtaposed with Rheb·GTP, and activated to drive downstream cellular responses.
Cell Metabolism  , DOI: ( /j.cmet )
Copyright © 2016 Elsevier Inc. Terms and Conditions