Reactome | v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP binds mTORC1

v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP binds mTORC1

Stable Identifier

R-HSA-9645608

Type

Reaction [binding]

Species

Homo sapiens

Compartment

lysosomal membrane

ReviewStatus

5/5

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v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP binds mTORC1

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The heterodimer comprising RRAGA,B:GTP and RRAGC,D:GDP (RagA:GTP or RagB:GTP complexed with RagC:GDP or RagD:GDP) forms the active conformation of the Rag complex that recruits the mTORC1 complex from the cytosol to the lysosomal membrane (Kim et al. 2008, Sancak et al. 2008, Sancak et al. 2010) where RHEB activates the protein kinase activity of mTORC1. Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 (Zoncu et al. 2011). The active state of the RRAGA,B:RRAGC,D heterodimer is less stably associated with the Ragulator complex and appears to cycle with mTORC1 between the lysosomal membrane and the cytosol (Lawrence et al. 2018). The cycling may provide a mechanism for attenuating mTORC1 signaling.

Literature References

PubMed ID	Title	Journal	Year
20381137	Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids Sabatini, DM, Zoncu, R, Sancak, Y, Bar-Peled, L, Nada, S, Markhard, AL	Cell	2010
22053050	mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase Sabatini, DM, Sancak, Y, Zoncu, R, Bar-Peled, L, Efeyan, A, Wang, S	Science	2011
18497260	The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1 Thoreen, CC, Shaul, YD, Sabatini, DM, Sancak, Y, Bar-Peled, L, Lindquist, RA, Peterson, TR	Science	2008
18604198	Regulation of TORC1 by Rag GTPases in nutrient response Guan, KL, Neufeld, TP, Kim, E, Goraksha-Hicks, P, Li, L	Nat. Cell Biol.	2008
30061680	A nutrient-induced affinity switch controls mTORC1 activation by its Rag GTPase-Ragulator lysosomal scaffold Rappold, R, Zoncu, R, Cho, KF, Kim, DJ, Hurley, JH, Moldavski, O, Tofaute, M, Lawrence, RE, Thrun, A	Nat. Cell Biol.	2018