FIGURE 2.

mTORC1 interacts with Rheb and Rag GTPases at the late endosomal/lysosomal membrane. The Ragulator complex is anchored to late endosomal/lysosomal membranes through p18, which is myristoylated and palmitoylated (12). The RagA/B-RagC/D complex binds to Ragulator, and when RagA/B is associated with GTP, it also binds to mTORC1 to recruit it to the membrane where it interacts with Rheb. Rheb is also subject to lipid modification (farnesylation), leading to its localization to intracellular membranes (reviewed in reference 45). The results of studies assessing TSC1/2 subcellular distribution have been inconsistent. However, a portion of the complex has been shown to interact with subcellular membranes (46). It seems likely that TSC1/2 interfaces with Rheb at the late endosomal/lysosomal membrane. c7orf59, chromosome 7 open reading frame 59; IGF-I, insulin-like growth factor I; mLST8, lethal with SEC13 protein 8; mTOR, mechanistic target of rapamycin; mTORC, mTOR complex; Rag, Ras-related GTP binding; raptor, regulatory-associated protein of mTOR, complex 1; Rheb, ras homolog enriched in brain; TBC1D7, ubiquitin specific peptide 6 (Trc-2)/budding uninhibited by benzimidazole/cell division cycle; TSC, tuberous sclerosis complex.