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. Author manuscript; available in PMC: 2014 Apr 16.
Published in final edited form as: Nat Rev Mol Cell Biol. 2013 Jan 30;14(3):133–139. doi: 10.1038/nrm3522

Figure 3. mTORC1 activation at the lysosome.

Figure 3

Amino acids are thought to accumulate within the lysosomal lumen and to signal to vacuolar H+-ATPase (v-ATPase) through an ‘inside–out’ mechanism. v-ATPase controls RAG GTPase–Ragulator binding, and therefore Ragulator guanine exchange factor (GEF) activity and RAGA and RAGB guanine nucleotide loading (RAGA/B·GTP). The active RAG complex (RAGA/B·GTP–RAGC/D·GDP) binds to mammalian target of rapamycin complex 1 (mTORC1) and recruits it to the lysosome, through an unknown mechanism, possibly in close proximity to RHEB (RAS homologue enriched in brain). Downstream of growth factor signalling, GTP-bound RHEB potently activates mTORC1.