Evidence map›Paper›PMID 41205175›Full record

ArticleCell reports2025

A retrograde, non-canonical integrated stress response cascade maintains synaptic strength under amino acid deprivation.

Megumi Mori, Grant Kauwe, Ammar Aly, Edward H Liao, Gary Scott, A Pejmun Haghighi

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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.

Megumi MoriThe Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Grant KauweThe Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Ammar AlyThe Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Edward H LiaoThe Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Gary ScottThe Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
A Pejmun HaghighiThe Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: phaghighi@buckinstitute.org.

Funding

Retrograde Regulation of Synaptic Strength by Translational MechanismsR01NS082793 · NINDS · BUCK INSTITUTE FOR RESEARCH ON AGING · PI HAGHIGHI, ALI PEJMUN · 2013 to 2022
$4.9M
NINDS NIH HHS R01 NS082793
6 · The paper itself

Abstract

Neuronal response to changes in nutrient availability is critical for maintaining metabolic homeostasis and organismal survival. Nevertheless, we know little about the molecular players that regulate and maintain neurotransmission under nutritional stress. We demonstrate that, under acute amino acid restriction, the maintenance of normal synaptic strength at the Drosophila larval neuromuscular junction critically depends on the integrated stress response (ISR) machinery. Our findings indicate that amino acid restriction triggers a non-canonical ISR cascade in muscle via GCN2 and eIF2α phosphorylation but independently of ATF4. We have identified Still life (Sif), an ortholog of human TIAM1, as a translational target of the ISR and show that it is required in muscle for mediating the action of the ISR. Our results reveal an intricate non-canonical ISR signaling cascade at the synapse and offer a new framework to separate the role of the ISR in proteostasis from its synaptic actions.

Indexed as

Amino AcidsDrosophila melanogasterStress, PhysiologicalSynapsesActivating Transcription Factor 4AnimalsDrosophila ProteinsEukaryotic Initiation Factor-2HumansLarvaNeuromuscular JunctionPhosphorylationProtein Serine-Threonine KinasesSignal TransductionSynaptic TransmissionActivating Transcription Factor 4Amino AcidsDrosophila ProteinsEukaryotic Initiation Factor-2Protein Serine-Threonine Kinasesamino acid sensingCP: metabolismCP: neuroscienceeIF2alphaGCN2integrated stress responsepresynaptic releaseregulation of translationretrograde signalingsynaptic set point

Identifiers

PMID41205175
PMCPMC12710418

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.