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. Author manuscript; available in PMC: 2015 Jul 1.
Published in final edited form as: Trends Cell Biol. 2014 Mar 31;24(7):400–406. doi: 10.1016/j.tcb.2014.03.003

Figure 1. The mTORC1 amino acid sensing pathway.

Figure 1

A. Under low amino acid conditions Ragulator is found in an inhibitory state with the v-ATPase and GATOR1 exerts its GAP activity towards RagA, keeping this GTPase in the inactive GDP-bound state that is not sufficient to recruit mTORC1. Insulin signaling inhibits TSC complex translocation to the lysosomal surface where it functions as a GAP for Rheb, inactivating this G protein. B. Upon amino acid stimulation, GATOR1 may be inhibited by GATOR2 and Ragulator and v-ATPase undergo a conformational change unleashing the GEF activity of Ragulator towards RagA, while the folliculin complex promotes RagC GTP hydrolysis. The now active heterodimer, consisting of GTP-bound RagA and GDP-loaded RagC, recruits mTORC1 to the lysosomal surface, where it interacts with and is activated by Rheb.