The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation

Mauricio M Oliveira; Muhaned Mohamed; Megan K Elder; Keylin Banegas-Morales; Maggie Mamcarz; Emily H Lu; Ela A N Golhan; Nishika Navrange; Snehajyoti Chatterjee; Ted Abel; Eric Klann

doi:10.1016/j.celrep.2023.113670

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The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation

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The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation

Mauricio M Oliveira, Muhaned Mohamed, Megan K Elder, Keylin Banegas-Morales, Maggie Mamcarz, Emily H Lu, Ela A N Golhan, Nishika Navrange, Snehajyoti Chatterjee, Ted Abel, …

Cell reports (Cambridge), Vol.43(2), 113670

02/01/2024

DOI: 10.1016/j.celrep.2023.113670

PMCID: PMC10964249

PMID: 38219147

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Abstract

Neuronal protein synthesis is required for long-lasting plasticity and long-term memory consolidation. Dephosphorylation of eukaryotic initiation factor 2α is one of the key translational control events that is required to increase de novo protein synthesis that underlies long-lasting plasticity and memory consolidation. Here, we interrogate the molecular pathways of translational control that are triggered by neuronal stimulation with brain-derived neurotrophic factor (BDNF), which results in eukaryotic initiation factor 2α (eIF2α) dephosphorylation and increases in de novo protein synthesis. Primary rodent neurons exposed to BDNF display elevated translation of GADD34, which facilitates eIF2α dephosphorylation and subsequent de novo protein synthesis. Furthermore, GADD34 requires G-actin generated by cofilin to dephosphorylate eIF2α and enhance protein synthesis. Finally, GADD34 is required for BDNF-induced translation of synaptic plasticity-related proteins. Overall, we provide evidence that neurons repurpose GADD34, an effector of the integrated stress response, as an orchestrator of rapid increases in eIF2-dependent translation in response to plasticity-inducing stimuli.

Cytoskeleton

Protein Synthesis

GADD34

eIF2α

neuronal plasticity

mRNA translation

BDNF

CP: Neuroscience

CP: Molecular biology

neuron

synaptic plasticity

local translation

Details

Title: Subtitle: The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation
Creators: Mauricio M Oliveira - New York University
Muhaned Mohamed - New York University
Megan K Elder - New York University
Keylin Banegas-Morales - New York University
Maggie Mamcarz - New York University
Emily H Lu - New York University
Ela A N Golhan - New York University
Nishika Navrange - New York University
Snehajyoti Chatterjee - University of Iowa
Ted Abel - University of Iowa
Eric Klann - New York University
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.43(2), 113670
DOI: 10.1016/j.celrep.2023.113670
PMID: 38219147
PMCID: PMC10964249
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Grant note: DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: NS122316; DOI: 10.13039/100000002, name: National Institutes of Health
Language: English
Date published: 02/01/2024
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984548410802771

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