Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival

Efeyan A, Sabatini DM et al. · 2012 · Nature · Atlas ID EFE2012

What this study shows

Rag-GTPase control of mTORC1 is essential for neonatal autophagy and survival to fasting.

Abstract

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The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates organismal growth in response to many environmental cues, including nutrients and growth factors. Cell-based studies showed that mTORC1 senses amino acids through the RagA-D family of GTPases (also known as RRAGA, B, C and D), but their importance in mammalian physiology is unknown. Here we generate knock-in mice that express a constitutively active form of RagA (RagA(GTP)) from its endogenous promoter. RagA(GTP/GTP) mice develop normally, but fail to survive postnatal day 1.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse (RagA GTP knock-in)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse (RagA GTP knock-in)
Journal	Nature
Year	2012
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1038/nature11745 · PMID 23263183 · Free full text (PMC4000705)

Extracted findings

Intervention	Genetic – constitutively active RagA(GTP) knock-in
Target	mTORC1 / Rag GTPases
Model	Mouse (RagA GTP knock-in)
Effect	Constitutive RagA→mTORC1 blocks fasting-induced autophagy in neonates → death on postnatal day 1 when fasted
Dose	not stated
Sample size	not stated
Effect size	Treatment of pups at birth with rapamycin significantly delayed the death of fasted RagA GTP/GTP neonates from ~14 h to ~21 h (p<0.01).
Limitations	not stated

Cite this paper

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Efeyan, A., et al. (2012). Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature. https://doi.org/10.1038/nature11745

@article{EFE2012,
  author       = {Efeyan, A. and Sabatini, D. M. and others},
  title        = {{Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival}},
  journal      = {Nature},
  year         = {2012},
  doi          = {10.1038/nature11745},
  note         = {PMID: 23263183},
}

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 EFE2012) [Data set]. https://mtor-atlas.org/study/EFE2012/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_EFE2012,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record EFE2012},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/EFE2012/},
  doi          = {10.5281/zenodo.22059963}
}