Evidence map›Paper›PMID 37698461›Full record

ArticleeLife2023

Continuous sensing of nutrients and growth factors by the mTORC1-TFEB axis.

Breanne Sparta, Nont Kosaisawe, Michael Pargett, Madhura Patankar, Nicholaus DeCuzzi, John G Albeck

Open access · goldAbstract read
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Breanne SpartaDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, United States.ORCID 0000-0002-8255-1409
Nont Kosaisawe *Department of Molecular and Cellular Biology, University of California, Davis, Davis, United States.ORCID 0000-0002-4710-1082
Michael Pargett *Department of Molecular and Cellular Biology, University of California, Davis, Davis, United States.ORCID 0000-0002-1403-7408
Madhura PatankarDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, United States.
Nicholaus DeCuzziDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, United States.
John G AlbeckDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, United States.ORCID 0000-0003-2688-8653
University of California, Davis · US

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI KC KENT LLOYD · 2002 to 2026
$84.9M
TRAINING IN COMPARATIVE LUNG BIOLOGY AND MEDICINET32HL007013 · NHLBI · UNIVERSITY OF CALIFORNIA DAVIS · PI Elena Goncharova, Nicholas J. KENYON · 1985 to 2026
$10.1M
UPLIFT: UCLA Postdocs' Longitudinal Investment in Faculty TrainingK12GM106996 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CAREY, MICHAEL F, VILLANUEVA, CLAUDIO J · 2016 to 2025
$7.1M
Control of gene expression by dynamic metabolic oscillationsR35GM139621 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ALBECK, JOHN G. · 2021 to 2025
$1.9M
The role of dynamics in defining the limits of normal developmental signaling.R01GM115650 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ALBECK, JOHN G. · 2016 to 2021
$1.8M
Defining the logic and function of the AMPK-mTORC1 signaling axisF31GM120937 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SPARTA, BREANNE · 2017 to 2018
$73k
NCI NIH HHS P30 CA093373NHLBI NIH HHS T32 HL007013NHLBI NIH HHS T32HL007013NIGMS NIH HHS F31 GM120937NIGMS NIH HHS F31GM120937NIGMS NIH HHS K12 GM106996NIGMS NIH HHS R01 GM115650NIGMS NIH HHS R01GM115650NIGMS NIH HHS R35 GM139621NIGMS NIH HHS R35GM139621
6 · The paper itself

Abstract

mTORC1 senses nutrients and growth factors and phosphorylates downstream targets, including the transcription factor TFEB, to coordinate metabolic supply and demand. These functions position mTORC1 as a central controller of cellular homeostasis, but the behavior of this system in individual cells has not been well characterized. Here, we provide measurements necessary to refine quantitative models for mTORC1 as a metabolic controller. We developed a series of fluorescent protein-TFEB fusions and a multiplexed immunofluorescence approach to investigate how combinations of stimuli jointly regulate mTORC1 signaling at the single-cell level. Live imaging of individual MCF10A cells confirmed that mTORC1-TFEB signaling responds continuously to individual, sequential, or simultaneous treatment with amino acids and the growth factor insulin. Under physiologically relevant concentrations of amino acids, we observe correlated fluctuations in TFEB, AMPK, and AKT signaling that indicate continuous activity adjustments to nutrient availability. Using partial least squares regression modeling, we show that these continuous gradations are connected to protein synthesis rate via a distributed network of mTORC1 effectors, providing quantitative support for the qualitative model of mTORC1 as a homeostatic controller and clarifying its functional behavior within individual cells.

Indexed as

Multiprotein ComplexesTOR Serine-Threonine KinasesAmino AcidsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsIntercellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 1NutrientsAmino AcidsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsIntercellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesNutrientsTOR Serine-Threonine KinasesAKTAMP-activated protein kinase (AMPK)cell biologycellular metabolismcomputational biologyglycogen synthase kinase 3 (GSK3)humannutrient sensingsystems biologytarget of rapamycin (mTOR)

Identifiers

PMID37698461
PMCPMC10547473
OpenAlexW4386624385

What Socratic 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 Socratic graph.