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Pathway link RAGULATOR-RAG

Ragulator Rag GTPases

Ragulator activates Rag GTPases.

Ragulator anchors the Rag proteins to the lysosome and also helps flip them into their "on" shape, together with a second protein, SLC38A9. Both jobs are shown in biochemical experiments.

Ragulator does two jobs on the Rags. It tethers the Rag heterodimer to the lysosomal surface, and it acts as an unusual exchange factor: first reported as a GEF for RagA/B (BAR2012), its exchange activity was later placed on RagC, where releasing GTP unlocks the inactive state (SHE2018B). Loading RagA with GTP is done by arginine-bound SLC38A9 (see SLC38A9-RAG).

The conditions it holds under

Human cells, Drosophila and purified recombinant proteins (BAR2012, SAN2010, SHE2018B). The exchange activity was first assigned to RagA/B and later to RagC, so the exact step is still being refined. Whole-animal and human relevance are not tested here.

Time it takes
always on
Step
direct (one molecule acts on the other)
Measured in
human cells
Where in the cell
lysosome
Reaches people?
plausible in people, not shown directly
How settled
settled in the literature

Studies behind it

YearEvidenceStudy
2012 M Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1BAR2012 Ragulator was reported as a guanine-nucleotide exchange factor for RagA/B on the lysosome; later work places Ragulator's exchange activity on RagC and assigns RagA GTP loading to SLC38A9, so the tethering role is the better-established one.
2010 M Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acidsSAN2010 Established WHERE mTORC1 gets switched on: the lysosome surface. Identified Ragulator as the lysosomal dock that recruits the Rag GTPases and drags mTORC1 to the membrane where its activator Rheb lives. Amino acids work by controlling this translocation.
2018 M Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanismsSHE2018B Ragulator and SLC38A9 each act as an unusual guanine-nucleotide exchange factor on the Rag heterodimer, and together they push it into its active state. Ragulator triggers GTP release from RagC, which unlocks the inactive configuration; arginine-bound SLC38A9 converts RagA from the GDP- to the GTP-loaded state. Boundary: purified proteins and cultured human cells. This is the biochemistry of the switch, not a measurement in tissue.

Points the other way

No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.

Who has checked this

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Curated by
Oliver Barton, with AI help for drafting; see how links are checked.

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