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G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling.
Prentzell, Mirja Tamara; Rehbein, Ulrike; Cadena Sandoval, Marti; De Meulemeester, Ann-Sofie; Baumeister, Ralf; Brohée, Laura; Berdel, Bianca; Bockwoldt, Mathias; Carroll, Bernadette; Chowdhury, Suvagata Roy; von Deimling, Andreas; Demetriades, Constantinos; Figlia, Gianluca; de Araujo, Mariana Eca Guimaraes; Heberle, Alexander M; Heiland, Ines; Holzwarth, Birgit; Huber, Lukas A; Jaworski, Jacek; Kedra, Magdalena; Kern, Katharina; Kopach, Andrii; Korolchuk, Viktor I; van 't Land-Kuper, Ineke; Macias, Matylda; Nellist, Mark; Palm, Wilhelm; Pusch, Stefan; Ramos Pittol, Jose Miguel; Reil, Michèle; Reintjes, Anja; Reuter, Friederike; Sampson, Julian R; Scheldeman, Chloë; Siekierska, Aleksandra; Stefan, Eduard; Teleman, Aurelio A; Thomas, Laura E; Torres-Quesada, Omar; Trump, Saskia; West, Hannah D; de Witte, Peter; Woltering, Sandra; Yordanov, Teodor E; Zmorzynska, Justyna; Opitz, Christiane A; Thedieck, Kathrin.
Affiliation
  • Prentzell MT; Brain 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
  • Rehbein U; Department 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 26
  • Cadena Sandoval M; Department 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
  • De Meulemeester AS; Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium.
  • Baumeister R; 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; Signalling Research Centres BIOSS and CIBSS & ZBMZ Center for Bioche
  • Brohée L; Cell Growth Control in Health and Age-Related Disease Group, Max Planck Institute for Biology of Ageing (MPI-AGE), Cologne 50931, Germany.
  • Berdel B; Brain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
  • Bockwoldt M; Department of Arctic and Marine Biology, UiT The Arctic University of Norway, Tromsø 9037, Norway.
  • Carroll B; School of Biochemistry, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
  • Chowdhury SR; Cell Signaling and Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
  • von Deimling A; German 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.
  • Demetriades C; Cell 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.
  • Figlia G; Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Heidelberg University, Heidelberg 69120, Germany.
  • de Araujo MEG; Institute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria.
  • Heberle AM; Department 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
  • Heiland I; Department of Arctic and Marine Biology, UiT The Arctic University of Norway, Tromsø 9037, Norway.
  • Holzwarth B; Department of Bioinformatics and Molecular Genetics (Faculty of Biology), University of Freiburg, Freiburg 79104, Germany.
  • Huber LA; Institute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria; Austrian Drug Screening Institute (ADSI), Innsbruck 6020, Austria.
  • Jaworski J; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
  • Kedra M; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
  • Kern K; Brain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
  • Kopach A; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
  • Korolchuk VI; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • van 't Land-Kuper I; Department 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 26
  • Macias M; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
  • Nellist M; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 GD, The Netherlands.
  • Palm W; Cell Signaling and Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
  • Pusch S; German 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.
  • Ramos Pittol JM; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
  • Reil M; Brain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
  • Reintjes A; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
  • Reuter F; Brain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
  • Sampson JR; Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University Medical School, Cardiff CF14 4AY, UK.
  • Scheldeman C; Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium; Neurogenetics Research Group, VUB, Brussels 1090, Belgium.
  • Siekierska A; Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium.
  • Stefan E; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
  • Teleman AA; Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Heidelberg University, Heidelberg 69120, Germany.
  • Thomas LE; Institute of Life Science, Swansea University, Swansea SA2 8PP, UK.
  • Torres-Quesada O; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.
  • Trump S; Molecular Epidemiology Unit, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin 13353, Germany.
  • West HD; Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University Medical School, Cardiff CF14 4AY, UK.
  • de Witte P; Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium.
  • Woltering S; Brain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
  • Yordanov TE; Institute 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.
  • Zmorzynska J; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.
  • Opitz CA; Brain 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 addres
  • Thedieck K; Department 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 26
Cell ; 184(3): 655-674.e27, 2021 02 04.
Article in En | MEDLINE | ID: mdl-33497611
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tuberous Sclerosis / Signal Transduction / RNA-Binding Proteins / DNA Helicases / RNA Helicases / Adaptor Proteins, Signal Transducing / RNA Recognition Motif Proteins / Mechanistic Target of Rapamycin Complex 1 / Poly-ADP-Ribose Binding Proteins / Lysosomes Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2021 Type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tuberous Sclerosis / Signal Transduction / RNA-Binding Proteins / DNA Helicases / RNA Helicases / Adaptor Proteins, Signal Transducing / RNA Recognition Motif Proteins / Mechanistic Target of Rapamycin Complex 1 / Poly-ADP-Ribose Binding Proteins / Lysosomes Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2021 Type: Article