Oliver's mTOR Atlas Evidence Platform
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G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling

Prentzell MT, Rehbein U, Cadena Sandoval M, De Meulemeester AS, Baumeister R, Brohée L, Berdel B, Bockwoldt M, Carroll B, Chowdhury SR, von Deimling A, …, Thedieck K · 2021 · Cell · Atlas ID PRE2021

What this study shows

Adds a physical brake upstream of mTORC1. G3BP1 and G3BP2, known until then as core stress-granule proteins, also sit on the cytoplasmic face of the lysosome and are what holds the TSC complex there; without them TSC cannot reach its target and mTORC1 becomes over-responsive to amino acids and insulin. Loss of G3BP1 reproduces TSC-like hyperactivity phenotypes: faster mTORC1-driven motility in breast cancer cells, with low G3BP1 correlating with worse patient outcome, and disturbed neuronal development in zebrafish. Relevant to the Atlas because it is a lysosomal tethering step that the canonical Rheb/TSC diagram does not show.

Abstract

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Ras GTPase-activating protein-binding proteins 1 and 2 (G3BP1 and G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface of lysosomes. They act in a non-redundant manner to anchor the tuberous sclerosis complex (TSC) protein complex to lysosomes and suppress activation of the metabolic master regulator mechanistic target of rapamycin complex 1 (mTORC1) by amino acids and insulin. Like the TSC complex, G3BP1 deficiency elicits phenotypes related to mTORC1 hyperactivity.

Read the full abstract on PubMed →

At a glance

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Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human and mouse cells; breast cancer patient data; zebrafish) 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 type5 - Mechanistic / In Vitro
Model systemHuman and mouse cells; breast cancer patient data; zebrafish
JournalCell
Year2021
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1016/j.cell.2020.12.024 · PMID 33497611

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

People in the Atlas

  • Mirja Tamara Prentzell first author · 2 studies in the Atlas

    First author of the study showing that G3BP proteins anchor the TSC complex to lysosomes, a physical brake on mTORC1; earlier co-author on the dynamic insulin–mTOR network model.

  • Kathrin Thedieck last author · 3 studies in the Atlas

    Senior author of three Atlas studies that treat mTOR signalling as a dynamic network: TSC-independent mTORC2 activation, concurrent AMPK and mTOR activation by amino acids, and G3BP tethering of TSC to lysosomes.

  • Ralf Baumeister 2 studies in the Atlas

    Head of the Freiburg department that hosted the Thedieck group during the mTOR network modelling work; co-author on the dynamic mTOR model and the G3BP–TSC study.

  • Laura Brohée 2 studies in the Atlas

    Cell biologist who studied how lipid metabolism and the lysosome feed into mTORC1, first at the University of Liège and then at the Max Planck Institute for Biology of Ageing in Cologne

  • Bernadette Carroll 3 studies in the Atlas

    First author of the study showing why mTORC1 stays switched on in senescent cells, and co-author on G3BP–TSC and senescence-mitophagy work; her own lab studies how nutrient sensing breaks down in ageing cells.

More: 42 other authors
  • Constantinos Demetriades 7 studies in the Atlas

    Showed as a postdoc in Aurelio Teleman's lab that starvation and other stresses pull TSC2 to the lysosome to switch mTORC1 off. His group, at the Max Planck Institute for Biology of Ageing in Cologne from 2017 and at ERIBA in Groningen since 2025, studies how cells sense nutrients and stress through mTORC1 and how this changes with age

  • Gianluca Figlia 2 studies in the Atlas

    Cell biologist who studied how mTORC1 senses nutrients in Aurelio Teleman's group at the German Cancer Research Center, including the finding that glutamine is sensed through the kinase GCN2, and who now works at the Institute of Neuropathology in Aachen

  • Mariana de Araujo 3 studies in the Atlas

    Cell biologist in Lukas Huber's group in Innsbruck who solved the crystal structure of the Ragulator (LAMTOR) complex, the lysosomal platform on which mTORC1 is switched on

  • Alexander M Heberle 2 studies in the Atlas

    Cell biologist and Junior Group Leader at the University of Innsbruck who studies how mTOR balances growth signalling and metabolism when cells are under stress, trained in Kathrin Thedieck's systems-biology group

  • Lukas A. Huber 4 studies in the Atlas

    Cell biologist who studied the p14-MP1 scaffold on late endosomes, a complex later recognised as part of Ragulator (LAMTOR), the lysosomal platform that holds mTORC1 in place

  • Viktor I. Korolchuk 5 studies in the Atlas

    Showed that where lysosomes sit inside the cell tunes mTORC1 activity to nutrient supply. His Newcastle lab found that senescent cells can no longer switch mTORC1 off when nutrients or growth factors are withdrawn, and studies how autophagy and mitophagy decline with age

  • Julian R. Sampson 2 studies in the Atlas

    Clinical geneticist who led the consortium that identified the TSC2 gene and led trials of mTOR inhibitors in tuberous sclerosis, including the TRON trial of everolimus for cognition.

  • Aurelio A. Teleman 5 studies in the Atlas

    Uses fruit-fly genetics and human cells to study how growth signalling through TOR controls cell and body size. His lab showed that starvation and other stresses move TSC2 to the lysosome to switch mTORC1 off

No profile yet: Rehbein U, Cadena Sandoval M, De Meulemeester AS, Berdel B, Bockwoldt M, Chowdhury SR, von Deimling A, Heiland I, Holzwarth B, Jaworski J, Kedra M, Kern K, Kopach A, van 't Land-Kuper I, Macias M, Nellist M, Palm W, Pusch S, Ramos Pittol JM, Reil M, Reintjes A, Reuter F, Scheldeman C, Siekierska A, Stefan E, Thomas LE, Torres-Quesada O, Trump S, West HD, de Witte P, Woltering S, Yordanov TE, Zmorzynska J, Opitz CA

Related studies

More related studies

All 212 studies on mTORC1

Topics

LysosomeTSC1/TSC2Breast cancermTORC1

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.

InterventionG3BP1/G3BP2 knockout/knockdown; G3bp1 inhibition in zebrafish
TargetG3BP1/2 tethering of the TSC complex to lysosomes; mTORC1
ModelHuman and mouse cells; zebrafish; breast cancer patient data (correlative)
EffectLoss of G3BPs releases TSC from lysosomes and makes mTORC1 hyperactive to amino acids and insulin.

Cite this paper

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Prentzell, M. T., Rehbein, U., Cadena Sandoval, M., De Meulemeester, A. S., Baumeister, R., Brohée, L., Berdel, B., Bockwoldt, M., Carroll, B., Chowdhury, S. R., von Deimling, A., Demetriades, C., Figlia, G., de Araujo, M. E. G., Heberle, A. M., Heiland, I., Holzwarth, B., Huber, L. A., Jaworski, J., Kedra, M., Kern, K., Kopach, A., Korolchuk, V. I., van 't Land-Kuper, I., Macias, M., Nellist, M., Palm, W., Pusch, S., Ramos Pittol, J. M., Reil, M., Reintjes, A., Reuter, F., Sampson, J. R., Scheldeman, C., Siekierska, A., Stefan, E., Teleman, A. A., Thomas, L. E., Torres-Quesada, O., Trump, S., West, H. D., de Witte, P., Woltering, S., Yordanov, T. E., Zmorzynska, J., Opitz, C. A., & Thedieck, K. (2021). G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. Cell. https://doi.org/10.1016/j.cell.2020.12.024

@article{PRE2021,
  author       = {Prentzell, M. T. and Rehbein, U. and Cadena Sandoval, M. and De Meulemeester, A. S. and Baumeister, R. and Brohée, L. and Berdel, B. and Bockwoldt, M. and Carroll, B. and Chowdhury, S. R. and von Deimling, A. and Demetriades, C. and Figlia, G. and de Araujo, M. E. G. and Heberle, A. M. and Heiland, I. and Holzwarth, B. and Huber, L. A. and Jaworski, J. and Kedra, M. and Kern, K. and Kopach, A. and Korolchuk, V. I. and van 't Land-Kuper, I. and Macias, M. and Nellist, M. and Palm, W. and Pusch, S. and Ramos Pittol, J. M. and Reil, M. and Reintjes, A. and Reuter, F. and Sampson, J. R. and Scheldeman, C. and Siekierska, A. and Stefan, E. and Teleman, A. A. and Thomas, L. E. and Torres-Quesada, O. and Trump, S. and West, H. D. and de Witte, P. and Woltering, S. and Yordanov, T. E. and Zmorzynska, J. and Opitz, C. A. and Thedieck, K.},
  title        = {{G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling}},
  journal      = {Cell},
  year         = {2021},
  doi          = {10.1016/j.cell.2020.12.024},
  note         = {PMID: 33497611},
}

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 PRE2021) [Data set]. https://mtor-atlas.org/study/PRE2021/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_PRE2021,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record PRE2021},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/PRE2021/},
  doi          = {10.5281/zenodo.22059963}
}
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