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Record W3122091881 · doi:10.1016/j.cell.2020.12.024

G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling

2021· article· en· W3122091881 on OpenAlexfundno aff
Mirja Tamara Prentzell, Ulrike Rehbein, Marti Cadena Sandoval, Ann‐Sofie De Meulemeester, Ralf Baumeister, Laura Brohée, Bianca Berdel, Mathias Bockwoldt, Bernadette Carroll, Suvagata Roy Chowdhury, Andreas von Deimling, Constantinos Demetriades, Gianluca Figlia, Mariana E. G. de Araújo, Alexander Martin Heberle, Ines Heiland, Birgit Holzwarth, Lukas A. Huber, Jacek Jaworski, Magdalena Kedra, Katharina Kern, Andrii Kopach, Viktor I. Korolchuk, Ineke Kuper, Matylda Macias, Mark Nellist, Wilhelm Palm, Stefan Pusch, José M. Ramos Pittol, Michèle Reil, Anja Reintjes, Friederike Reuter, Julian R. Sampson, Chloë Scheldeman, Aleksandra Siekierska, Eduard Stefan, Aurelio A. Teleman, Laura E. Thomas, Omar Torres‐Quesada, Saskia Trump, Hannah D. West, Peter de Witte, Sandra Woltering, Teodor E. Yordanov, Justyna Zmorzyńska, Christiane A. Opitz, Kathrin Thedieck

Bibliographic record

VenueCell · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPI3K/AKT/mTOR signaling in cancer
Canadian institutionsnot available
FundersHorizon 2020Vlaamse regeringKU LeuvenFonds Wetenschappelijk OnderzoekAustrian Science FundMax-Planck-GesellschaftRijksuniversiteit GroningenEuropean Research CouncilMinisterstwo Edukacji i NaukiDeutsche ForschungsgemeinschaftUniversity of BristolFundacja na rzecz Nauki PolskiejMedizinische Universität InnsbruckEuropean CommissionStichting TSC FondsEuropean Molecular Biology OrganizationMedical Research CouncilDepartment of Health and Social CareAcademy of Medical SciencesWellcome TrustHeart of England NHS Foundation TrustCancer Research UKMinistère de l'Économie, de la Science et de l'Innovation - QuébecBritish Skin FoundationUniversität InnsbruckBundesministerium für Bildung und ForschungNational Institute for Health and Care ResearchTuberous Sclerosis AssociationTuberous Sclerosis AllianceDeutsches Krebsforschungszentrum
KeywordsmTORC1BiologyRHEBCell biologyTSC2RegulatorStress granuleZebrafishCrosstalkPI3K/AKT/mTOR pathwaySignal transductionBiochemistryGene

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.257
Teacher spread0.240 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations150
Published2021
Admission routes1
Has abstractno

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