Evidence mapPaperPMID 39103493Full record

ArticleThe EMBO journal2024

Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition.

Gabriel Talaia, Amanda Bentley-DeSousa, Shawn M Ferguson

Abstract read
In one paragraph

Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Gabriel TalaiaDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT, 06510, USA.ORCID http://orcid.org/0000-0003-1870-4658
Amanda Bentley-DeSousaDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT, 06510, USA.
Shawn M FergusonDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT, 06510, USA. shawn.ferguson@yale.edu.ORCID http://orcid.org/0000-0002-3092-7718

Funding

Molecular mechanisms that match lysosome function to cellular demandR01GM105718 · NIGMS · YALE UNIVERSITY · PI SHAWN FERGUSON · 2022 to 2022
$343k
Aligning Science Across Parkinson's (ASAP) ASAP-000580HHS | NIH | National Institute of General Medical Sciences (NIGMS) GM105718Michael J. Fox Foundation for Parkinson's Research (MJFF) ASAP-000580NIGMS NIH HHS R01 GM105718
6 · The paper itself

Abstract

Lysosomes play a pivotal role in coordinating macromolecule degradation and regulating cell growth and metabolism. Despite substantial progress in identifying lysosomal signaling proteins, understanding the pathways that synchronize lysosome functions with changing cellular demands remains incomplete. This study uncovers a role for TANK-binding kinase 1 (TBK1), well known for its role in innate immunity and organelle quality control, in modulating lysosomal responsiveness to nutrients. Specifically, we identify a pool of TBK1 that is recruited to lysosomes in response to elevated amino acid levels. This lysosomal TBK1 phosphorylates Rab7 on serine 72. This is critical for alleviating Rab7-mediated inhibition of amino acid-dependent mTORC1 activation. Furthermore, a TBK1 mutant (E696K) associated with amyotrophic lateral sclerosis and frontotemporal dementia constitutively accumulates at lysosomes, resulting in elevated Rab7 phosphorylation and increased mTORC1 activation. This data establishes the lysosome as a site of amino acid regulated TBK1 signaling that is crucial for efficient mTORC1 activation. This lysosomal pool of TBK1 has broader implications for lysosome homeostasis, and its dysregulation could contribute to the pathogenesis of ALS-FTD.

Indexed as

Amino AcidsLysosomesMechanistic Target of Rapamycin Complex 1Protein Serine-Threonine Kinasesrab7 GTP-Binding ProteinsAmyotrophic Lateral SclerosisFrontotemporal DementiaHEK293 CellsHumansPhosphorylationrab GTP-Binding ProteinsSignal TransductionAmino AcidsMechanistic Target of Rapamycin Complex 1Protein Serine-Threonine Kinasesrab7 GTP-Binding Proteinsrab7 GTP-binding proteins, humanrab GTP-Binding ProteinsTBK1 protein, humanALS-FTDLysosomemTORC1Nutrient SensingTBK1

Identifiers

PMID39103493
PMCPMC11405869

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.