A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids

Gollwitzer P, Grützmacher N, Wilhelm S, Kümmel D, Demetriades C · 2022 · Nature Cell Biology · Atlas ID GOL2022

What this study shows

The four mammalian Rag GTPase paralogues are not functionally interchangeable: RagC/D determines substrate specificity (RagD favors TFEB/TFE3 phosphorylation via tighter LAMTOR binding), while RagA/B determines the response to amino acid withdrawal (RagB-expressing cells keep mTORC1 lysosomal and active even upon starvation). Author correction issued 2023 (PMID 36536178, no change to conclusions).

Abstract

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Amino acid availability controls mTORC1 activity via a heterodimeric Rag GTPase complex that functions as a scaffold at the lysosomal surface, bringing together mTORC1 with its activators and effectors. Mammalian cells express four Rag proteins (RagA-D) that form dimers composed of RagA/B bound to RagC/D. Traditionally, the Rag paralogue pairs (RagA/B and RagC/D) are referred to as functionally redundant, with the four dimer combinations used interchangeably in most studies.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cells (genetically modified Rag-paralogue cell lines)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Human cells (genetically modified Rag-paralogue cell lines)
Journal	Nature Cell Biology
Year	2022
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1038/s41556-022-00976-y · PMID 36097072

Cite this paper

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Gollwitzer, P., Grützmacher, N., Wilhelm, S., Kümmel, D., & Demetriades, C. (2022). A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids. Nature Cell Biology. https://doi.org/10.1038/s41556-022-00976-y

@article{GOL2022,
  author       = {Gollwitzer, P. and Grützmacher, N. and Wilhelm, S. and Kümmel, D. and Demetriades, C.},
  title        = {{A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids}},
  journal      = {Nature Cell Biology},
  year         = {2022},
  doi          = {10.1038/s41556-022-00976-y},
  note         = {PMID: 36097072},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record GOL2022) [Data set]. https://mtor-atlas.org/study/GOL2022/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_GOL2022,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record GOL2022},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/GOL2022/},
  doi          = {10.5281/zenodo.22059963}
}