Journal article
The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation
Cell reports (Cambridge), Vol.43(2), 113670
02/01/2024
DOI: 10.1016/j.celrep.2023.113670
PMCID: PMC10964249
PMID: 38219147
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.
Details
- Title: Subtitle
- The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation
- Creators
- Mauricio M Oliveira - New York UniversityMuhaned Mohamed - New York UniversityMegan K Elder - New York UniversityKeylin Banegas-Morales - New York UniversityMaggie Mamcarz - New York UniversityEmily H Lu - New York UniversityEla A N Golhan - New York UniversityNishika Navrange - New York UniversitySnehajyoti Chatterjee - University of IowaTed Abel - University of IowaEric 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
- 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
Metrics
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