Evidence map›Paper›PMID 35913999›Full record

ArticlePLoS genetics2022

The Rab GTPase activating protein TBC-2 regulates endosomal localization of DAF-16 FOXO and lifespan.

İçten Meraş, Laëtitia Chotard, Thomas Liontis, Zakaria Ratemi, Benjamin Wiles, Jung Hwa Seo, Jeremy M Van Raamsdonk, Christian E Rocheleau

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 50% of its field
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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

İçten MeraşDepartment of Anatomy and Cell Biology, McGill University, Montreal, Canada.
Laëtitia ChotardDivision of Endocrinology and Metabolism, Department of Medicine, McGill University, Montreal, Canada.
Thomas LiontisMetabolic Disorders and Complications Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Canada.ORCID 0000-0003-3376-1511
Zakaria RatemiMetabolic Disorders and Complications Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Canada.
Benjamin WilesMetabolic Disorders and Complications Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Canada.
Jung Hwa SeoMetabolic Disorders and Complications Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Canada.
Jeremy M Van RaamsdonkMetabolic Disorders and Complications Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Canada.
Christian E RocheleauDepartment of Anatomy and Cell Biology, McGill University, Montreal, Canada.ORCID 0000-0001-6738-5636
McGill University Health Centre · CAMcGill University · CA

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Ann E. Rougvie · 2012 to 2026
$7.5M
Molecular mechanisms by which mild elevation of mitochondrial superoxide extends lifespanR01GM121756 · NIGMS · VAN ANDEL RESEARCH INSTITUTE · PI VAN RAAMSDONK, JEREMY MICHAEL · 2017 to 2021
$1.3M
CIHR PJT-159725CIHR PJT-399148CIHR PJT-416150NIGMS NIH HHS R01 GM121756NIH HHS P40 OD010440
6 · The paper itself

Abstract

FOXO transcription factors have been shown to regulate longevity in model organisms and are associated with longevity in humans. To gain insight into how FOXO functions to increase lifespan, we examined the subcellular localization of DAF-16 in C. elegans. We show that DAF-16 is localized to endosomes and that this endosomal localization is increased by the insulin-IGF signaling (IIS) pathway. Endosomal localization of DAF-16 is modulated by endosomal trafficking proteins. Disruption of the Rab GTPase activating protein TBC-2 increases endosomal localization of DAF-16, while inhibition of TBC-2 targets, RAB-5 or RAB-7 GTPases, decreases endosomal localization of DAF-16. Importantly, the amount of DAF-16 that is localized to endosomes has functional consequences as increasing endosomal localization through mutations in tbc-2 reduced the lifespan of long-lived daf-2 IGFR mutants, depleted their fat stores, and DAF-16 target gene expression. Overall, this work identifies endosomal localization as a mechanism regulating DAF-16 FOXO, which is important for its functions in metabolism and aging.

Indexed as

LongevityAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsForkhead Transcription FactorsGTPase-Activating ProteinsHumansInsulinMutationrab GTP-Binding ProteinsCaenorhabditis elegans Proteinsdaf-16 protein, C elegansForkhead Transcription FactorsGTPase-Activating ProteinsInsulinrab GTP-Binding ProteinsTBC-2 protein, C elegans

Identifiers

PMID35913999
PMCPMC9371356
OpenAlexW4289262513

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.