G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling.

Adaptor Proteins, Signal Transducing / metabolism Amino Acid Sequence Animals Breast Neoplasms / metabolism Cell Line, Tumor Cell Movement / drug effects Cytoplasmic Granules / drug effects DNA Helicases / chemistry Evolution, Molecular Female Humans Insulin / pharmacology Lysosomal Membrane Proteins / metabolism Lysosomes / drug effects Mechanistic Target of Rapamycin Complex 1 / metabolism Neurons / drug effects Phenotype Poly-ADP-Ribose Binding Proteins / chemistry RNA Helicases / chemistry RNA Recognition Motif Proteins / chemistry RNA-Binding Proteins / metabolism Rats, Wistar Signal Transduction / drug effects Tuberous Sclerosis / metabolism Zebrafish / metabolism
G3BP1 G3BP2 TSC complex cancer lysosome mTORC1 metabolism neuronal function stress granule

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
04 02 2021
Historique:
received: 01 04 2020
revised: 03 11 2020
accepted: 14 12 2020
pubmed: 27 1 2021
medline: 25 8 2021
entrez: 26 1 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.cell.2020.12.024 PMID: 33497611 PMC: PMC7868890
pubmed: 33497611
pii: S0092-8674(20)31694-9
doi: 10.1016/j.cell.2020.12.024
pmc: PMC7868890
pii:
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
G3BP2 protein, human 0
Insulin 0
Lysosomal Membrane Proteins 0
Poly-ADP-Ribose Binding Proteins 0
RNA Recognition Motif Proteins 0
RNA-Binding Proteins 0
Mechanistic Target of Rapamycin Complex 1 EC 2.7.11.1
DNA Helicases EC 3.6.4.-
G3BP1 protein, human EC 3.6.4.12
RNA Helicases EC 3.6.4.13

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

655-674.e27

Subventions

Organisme : Medical Research Council
ID : MC_PC_16035
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Mirja Tamara 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, 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 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 26129, Germany; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.

Marti 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.

Ann-Sofie De Meulemeester (AS)

Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium.

Ralf 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 Biochemistry and Molecular Cell Research (Faculty of Medicine), University of Freiburg, Freiburg 79104, Germany.

Laura Brohée (L)

Cell Growth Control in Health and Age-Related Disease Group, Max Planck Institute for Biology of Ageing (MPI-AGE), Cologne 50931, Germany.

Bianca Berdel (B)

Brain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

Mathias Bockwoldt (M)

Department of Arctic and Marine Biology, UiT The Arctic University of Norway, Tromsø 9037, Norway.

Bernadette Carroll (B)

School of Biochemistry, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.

Suvagata Roy Chowdhury (SR)

Cell Signaling and Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

Andreas 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.

Constantinos 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.

Gianluca Figlia (G)

Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Heidelberg University, Heidelberg 69120, Germany.

Mariana Eca Guimaraes de Araujo (MEG)

Institute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria.

Alexander M 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.

Ines Heiland (I)

Department of Arctic and Marine Biology, UiT The Arctic University of Norway, Tromsø 9037, Norway.

Birgit Holzwarth (B)

Department of Bioinformatics and Molecular Genetics (Faculty of Biology), University of Freiburg, Freiburg 79104, Germany.

Lukas A Huber (LA)

Institute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria; Austrian Drug Screening Institute (ADSI), Innsbruck 6020, Austria.

Jacek Jaworski (J)

Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.

Magdalena Kedra (M)

Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.

Katharina Kern (K)

Brain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

Andrii Kopach (A)

Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.

Viktor I Korolchuk (VI)

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Ineke 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 26129, Germany.

Matylda Macias (M)

Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.

Mark Nellist (M)

Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 GD, The Netherlands.

Wilhelm Palm (W)

Cell Signaling and Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

Stefan 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.

Jose Miguel Ramos Pittol (JM)

Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.

Michèle Reil (M)

Brain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

Anja Reintjes (A)

Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.

Friederike Reuter (F)

Brain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

Julian R Sampson (JR)

Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University Medical School, Cardiff CF14 4AY, UK.

Chloë 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.

Aleksandra Siekierska (A)

Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium.

Eduard Stefan (E)

Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.

Aurelio A Teleman (AA)

Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Heidelberg University, Heidelberg 69120, Germany.

Laura E Thomas (LE)

Institute of Life Science, Swansea University, Swansea SA2 8PP, UK.

Omar Torres-Quesada (O)

Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria.

Saskia 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.

Hannah D West (HD)

Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University Medical School, Cardiff CF14 4AY, UK.

Peter de Witte (P)

Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven BE-3000, Belgium.

Sandra Woltering (S)

Brain Cancer Metabolism Group, German Consortium of Translational Cancer Research (DKTK) & German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

Teodor E 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.

Justyna Zmorzynska (J)

Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Warsaw 02-109, Poland.

Christiane A 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 address: c.opitz@dkfz.de.

Kathrin 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 26129, Germany; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria. Electronic address: kathrin.thedieck@uibk.ac.at.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Eucaryotes › Animaux › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Phénomènes physiologiques › Mouvement cellulaire › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Vésicules cytoplasmiques › Granulations cytoplasmiques › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Isomerases › Helicase › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Phénomènes biologiques › Évolution biologique › Évolution moléculaire › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones pancréatiques › Insulines › Insuline › G3BPs tether the TSC complex to lysosomes and...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Vésicules cytoplasmiques › Lysosomes › G3BPs tether the TSC complex to lysosomes and...
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