Evidence map›Paper›PMID 22574197›Full record

ArticlePloS one2012

Proton-assisted amino acid transporter PAT1 complexes with Rag GTPases and activates TORC1 on late endosomal and lysosomal membranes.

Margrét H Ögmundsdóttir, Sabine Heublein, Shubana Kazi, Bruno Reynolds, Shivanthy M Visvalingam, Michael K Shaw, Deborah C I Goberdhan

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
6.4field-weighted citation impact, top 2% 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

83 citing papers in PubMed, 133 citations in OpenAlex.

  1. Trial
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  13. FastiScience · 2023
    Article
  14. Review
  15. Review
  16. Article
  17. SNAT7 regulates mTORC1 via macropinocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  18. Review
  19. Lysosomes at the Crossroads of Cell Metabolism, Cell Cycle, and Stemness.International journal of molecular sciences · 2022
    Review
  20. Effects of Dietary Chlorogenic Acid Supplementation Derived fromOxidative medicine and cellular longevity · 2022
    Article

23 more citing papers are in PubMed but not listed here.

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

7 authors at 1 institution in 1 country.

Margrét H ÖgmundsdóttirDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Sabine Heublein
Shubana Kazi
Bruno Reynolds
Shivanthy M Visvalingam
Michael K Shaw
Deborah C I Goberdhan
University of Oxford · GB

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UK C19591/A6181Cancer Research UK C19591/A9093Cancer Research UK C38302/A12278Cancer Research UK C7713/A6174
6 · The paper itself

Abstract

Mammalian Target of Rapamycin Complex 1 (mTORC1) is activated by growth factor-regulated phosphoinositide 3-kinase (PI3K)/Akt/Rheb signalling and extracellular amino acids (AAs) to promote growth and proliferation. These AAs induce translocation of mTOR to late endosomes and lysosomes (LELs), subsequent activation via mechanisms involving the presence of intralumenal AAs, and interaction between mTORC1 and a multiprotein assembly containing Rag GTPases and the heterotrimeric Ragulator complex. However, the mechanisms by which AAs control these different aspects of mTORC1 activation are not well understood. We have recently shown that intracellular Proton-assisted Amino acid Transporter 1 (PAT1)/SLC36A1 is an essential mediator of AA-dependent mTORC1 activation. Here we demonstrate in Human Embryonic Kidney (HEK-293) cells that PAT1 is primarily located on LELs, physically interacts with the Rag GTPases and is required for normal AA-dependent mTOR relocalisation. We also use the powerful in vivo genetic methodologies available in Drosophila to investigate the regulation of the PAT1/Rag/Ragulator complex. We show that GFP-tagged PATs reside at both the cell surface and LELs in vivo, mirroring PAT1 distribution in several normal mammalian cell types. Elevated PI3K/Akt/Rheb signalling increases intracellular levels of PATs and synergistically enhances PAT-induced growth via a mechanism requiring endocytosis. In light of the recent identification of the vacuolar H(+)-ATPase as another Rag-interacting component, we propose a model in which PATs function as part of an AA-sensing engine that drives mTORC1 activation from LEL compartments.

Indexed as

Amino AcidsAmino Acid Transport SystemsAnimalsDrosophila melanogasterEndocytosisEndosomesFemaleGTP PhosphohydrolasesHEK293 CellsHumansIntracellular MembranesLysosomesMechanistic Target of Rapamycin Complex 1Monomeric GTP-Binding ProteinsMultiprotein ComplexesNeuropeptidesAmino AcidsAmino Acid Transport SystemsGTP PhosphohydrolasesMechanistic Target of Rapamycin Complex 1Monomeric GTP-Binding ProteinsMultiprotein ComplexesNeuropeptidesPhosphatidylinositol 3-KinasesProteinsProto-Oncogene Proteins c-aktRas Homolog Enriched in Brain ProteinRHEB protein, humanSLC36A1 protein, humanSymportersTOR Serine-Threonine Kinases

Identifiers

PMID22574197
PMCPMC3344915
OpenAlexW1986868498

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.