Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome

Menon S, Dibble CC, Talbott G, Hoxhaj G, Valvezan AJ, Takahashi H, Cantley LC, Manning BD · 2014 · Cell · Atlas ID MEN2014

What this study shows

Spatial control of the TSC complex integrates insulin and nutrient inputs at the lysosome.

Abstract

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mTORC1 promotes cell growth in response to nutrients and growth factors. Insulin activates mTORC1 through the PI3K-Akt pathway, which inhibits the TSC1-TSC2-TBC1D7 complex (the TSC complex) to turn on Rheb, an essential activator of mTORC1. However, the mechanistic basis of how this pathway integrates with nutrient-sensing pathways is unknown. We demonstrate that insulin stimulates acute dissociation of the TSC complex from the lysosomal surface, where subpopulations of Rheb and mTORC1 reside.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mammalian cells) 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	Mammalian cells
Journal	Cell
Year	2014
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.cell.2013.11.049 · PMID 24529379 · Free full text (PMC4030681)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Genetic/biochemical (TSC complex/Rheb)
Target	TSC complex / Rheb / mTORC1
Model	Mammalian cells
Effect	Insulin drives lysosomal dissociation of the TSC complex, integrating insulin and nutrient regulation of mTORC1

In the Atlas

Links in the pathway map

Supports Energy & cellular stress recruits TSC1/TSC2

Learn the biology

Want to understand the biology behind this study? → The TSC Complex — Where the Inputs Meet

Cite this paper

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Menon, S., Dibble, C. C., Talbott, G., Hoxhaj, G., Valvezan, A. J., Takahashi, H., Cantley, L. C., & Manning, B. D. (2014). Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell. https://doi.org/10.1016/j.cell.2013.11.049

@article{MEN2014,
  author       = {Menon, S. and Dibble, C. C. and Talbott, G. and Hoxhaj, G. and Valvezan, A. J. and Takahashi, H. and Cantley, L. C. and Manning, B. D.},
  title        = {{Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome}},
  journal      = {Cell},
  year         = {2014},
  doi          = {10.1016/j.cell.2013.11.049},
  note         = {PMID: 24529379},
}

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 MEN2014) [Data set]. https://mtor-atlas.org/study/MEN2014/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_MEN2014,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record MEN2014},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/MEN2014/},
  doi          = {10.5281/zenodo.22059963}
}

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