ArticleCell2021
G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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91citing papers in PubMed
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91 citing papers in PubMed, 144 citations in OpenAlex.
- G3BP1 depletion, observed in Parkinson's Disease, drives Golgi-lysosome-autophagy defects.Cell death and differentiation · 2026Article
- G3BP1 Succinylation at K413 is Critical for Cardiac Function by Modulating PI3K-AKT-mTOR Signal Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Global cellular responses to lysosomal damage.Current biology : CB · 2026Review
- YIF1A activates mTORC1 signaling to promote cellular senescence.Cell death & disease · 2026Article
- Resveratrol offers therapeutic potential in obesity-related osteoarthritis by targeting ferroptosis via G3BP1-SGs/mTOR modulation.Communications biology · 2026Article
- GRASP55 maintains lysosome function by controlling sorting of lysosomal enzymes at the Golgi.EMBO reports · 2026Article
- G3BP1 is a SWI/SNF-bound regulator of transcription that modulates activation of STATs.Bioscience reports · 2026Article
- Proteolytic cleavage of G3BP1 by calpain 1 couples NMDAR activation to mTOR-dependent local translation.EMBO reports · 2026Article
- The Role of Stress Granules in Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026Review
- Benchmarking Lysosome Enrichment Methods: A Guide for Research and Clinical Translation.Analytical chemistry · 2026Article
- Cross-kingdom miRNA delivery by Panax notoginseng-derived extracellular-like nanoparticles vesicles restores neuronal function after ischemic injury.Journal of nanobiotechnology · 2026Article
- Research Progress on the Biological Function, Disease-Driving Mechanism and Clinical Targeting Strategies of G3BP2.Molecules (Basel, Switzerland) · 2026Review
- A step-by-step guide to performing cancer metabolism research using custom-made media.Life science alliance · 2026Article
- Review
- Lysosomal membrane homeostasis and its importance in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Single-cell perturbations decipher ribosomal stress-surveillance regulators in type 2 diabetes.Nature metabolism · 2026Article
- Stress granule dynamics govern TOR reactivation and growth recovery during post-heat stress adaptation.Science advances · 2025Article
- Review
- AKT-mediated phosphorylation of TSC2 controls stimulus- and tissue-specific mTORC1 signaling and organ growth.Developmental cell · 2025Article
- Cellular homeostatic responses to lysosomal damage.Trends in cell biology · 2025Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
48 authors at 18 institutions in 8 countries.
Mirja Tamara PrentzellBrain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Department of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands; Department of Bioinformatics and Molecular Genetics (Faculty of Biology), University of Freiburg, Freiburg 79104, Germany; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg 79104, Germany.
Ulrike RehbeinDepartment of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands; Department for Neuroscience, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg 26129, Germany; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
Marti Cadena SandovalDepartment of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
Ann-Sofie De MeulemeesterLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium.
Ralf BaumeisterDepartment of Bioinformatics and Molecular Genetics (Faculty of Biology), University of Freiburg, Freiburg 79104, Germany; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg 79104, Germany; Signalling Research Centres BIOSS and CIBSS & ZBMZ Center for Biochemistry and Molecular Cell Research (Faculty of Medicine), University of Freiburg, Freiburg 79104, Germany.
Laura BrohéeCell Growth Control in Health and Age-Related Disease Group, Max Planck Institute for Biology of Ageing (MPI-AGE), Cologne 50931, Germany.
Bianca BerdelBrain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Mathias BockwoldtDepartment of Arctic and Marine Biology, UiT The Arctic University of Norway, Tromsø 9037, Norway.
Bernadette CarrollSchool of Biochemistry, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
Suvagata Roy ChowdhuryCell Signaling and Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Andreas von DeimlingGerman Consortium of Translational Cancer Research (DKTK), Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Department of Neuropathology, Institute of Pathology, Heidelberg University, Heidelberg 69120, Germany.
Constantinos DemetriadesCell Growth Control in Health and Age-Related Disease Group, Max Planck Institute for Biology of Ageing (MPI-AGE), Cologne 50931, Germany; CECAD Cluster of Excellence, University of Cologne, Cologne 50931, Germany.
Gianluca FigliaSignal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Heidelberg University, Heidelberg 69120, Germany.
Genomics England Research Consortium
Mariana Eca Guimaraes de AraujoInstitute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria.
Alexander M HeberleDepartment of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
Ines HeilandDepartment of Arctic and Marine Biology, UiT The Arctic University of Norway, Tromsø 9037, Norway.
Birgit HolzwarthDepartment of Bioinformatics and Molecular Genetics (Faculty of Biology), University of Freiburg, Freiburg 79104, Germany.
Lukas A HuberInstitute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria; Austrian Drug Screening Institute (ADSI), Innsbruck 6020, Austria.
Jacek JaworskiLaboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
Magdalena KedraLaboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
Katharina KernBrain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Andrii KopachLaboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
Viktor I KorolchukBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Ineke van 't Land-KuperDepartment of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands; Department for Neuroscience, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg 26129, Germany.
Matylda MaciasLaboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
Mark NellistDepartment of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 GD, The Netherlands.
Wilhelm PalmCell Signaling and Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Stefan PuschGerman Consortium of Translational Cancer Research (DKTK), Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Department of Neuropathology, Institute of Pathology, Heidelberg University, Heidelberg 69120, Germany.
Jose Miguel Ramos PittolInstitute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
Michèle ReilBrain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Anja ReintjesInstitute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
Friederike ReuterBrain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Julian R SampsonInstitute of Medical Genetics, Division of Cancer and Genetics, Cardiff University Medical School, Cardiff CF14 4AY, UK.
Chloë ScheldemanLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium; Neurogenetics Research Group, VUB, Brussels 1090, Belgium.
Aleksandra SiekierskaLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium.
Eduard StefanInstitute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
Aurelio A TelemanSignal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Heidelberg University, Heidelberg 69120, Germany.
Laura E ThomasInstitute of Life Science, Swansea University, Swansea SA2 8PP, UK.
Omar Torres-QuesadaInstitute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
Saskia TrumpMolecular Epidemiology Unit, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin 13353, Germany.
Hannah D WestInstitute of Medical Genetics, Division of Cancer and Genetics, Cardiff University Medical School, Cardiff CF14 4AY, UK.
Peter de WitteLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium.
Sandra WolteringBrain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Teodor E YordanovInstitute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria; Division of Cell and Developmental Biology, Institute for Molecular Bioscience, University of Queensland, St Lucia QLD 4072, Australia.
Justyna ZmorzynskaLaboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
Christiane A OpitzBrain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Department of Neurology, University Hospital Heidelberg and National Center for Tumor Diseases, Heidelberg 69120, Germany. Electronic address: c.opitz@dkfz.de.
Kathrin ThedieckDepartment of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands; Department for Neuroscience, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg 26129, Germany; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria. Electronic address: kathrin.thedieck@uibk.ac.at.
German Cancer Research Center · DEInternational Institute of Molecular and Cell Biology · PLUniversität Innsbruck · ATCarl von Ossietzky Universität Oldenburg · DEInnsbruck Medical University · ATKU Leuven · BEUniversity Medical Center Groningen · NLCardiff University · GBUiT The Arctic University of Norway · NOUniversity of Freiburg · DEErasmus MC · NLFujirebio (Belgium) · BEHumboldt-Universität zu Berlin · DEMax Planck Institute for Biology of Ageing · DENewcastle University · GBSwansea University · GBUniversity of Bristol · GBUniversity of Cologne · DE
Funding
Austrian Science Fund FWF P 32608Cancer Research UKMedical Research Council MC_PC_16035
Abstract
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. In the context of tumors, low G3BP1 levels enhance mTORC1-driven breast cancer cell motility and correlate with adverse outcomes in patients. Furthermore, G3bp1 inhibition in zebrafish disturbs neuronal development and function, leading to white matter heterotopia and neuronal hyperactivity. Thus, G3BPs are not only core components of SGs but also a key element of lysosomal TSC-mTORC1 signaling.
Indexed as
Signal TransductionAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsBreast NeoplasmsCell Line, TumorCell MovementCytoplasmic GranulesDNA HelicasesEvolution, MolecularFemaleHumansInsulinLysosomal Membrane ProteinsLysosomesMechanistic Target of Rapamycin Complex 1Adaptor Proteins, Signal TransducingDNA HelicasesG3BP1 protein, humanG3BP2 protein, humanInsulinLysosomal Membrane ProteinsMechanistic Target of Rapamycin Complex 1Poly-ADP-Ribose Binding ProteinsRNA-Binding ProteinsRNA HelicasesRNA Recognition Motif ProteinscancerG3BP1G3BP2lysosomemetabolismmTORC1neuronal functionstress granuleTSC complex
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