ArticleMolecular cell2019
Noncanonical Modulation of the eIF2 Pathway Controls an Increase in Local Translation during Neural Wiring.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 108 citations in OpenAlex.
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- Regulation of Subcellular Protein Synthesis for Restoring Neural Connectivity.International journal of molecular sciences · 2025Review
- Orchestrating Neural Development Through mRNA Translation Regulation.Journal of neurochemistry · 2025Review
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Emerging Molecular-Genetic Families in Dystonia: Endosome-Autophagosome-Lysosome and Integrated Stress Response Pathways.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- The integrated stress response in brain diseases: A double-edged sword for proteostasis and synapses.Current opinion in neurobiology · 2024Review
- CPEB2-activated axonal translation of VGLUT2 mRNA promotes glutamatergic transmission and presynaptic plasticity.Journal of biomedical science · 2024Article
- Mutation of the ALS-/FTD-Associated RNA-Binding Protein FUS Affects Axonal Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- The intersection of sleep and synaptic translation in synaptic plasticity deficits in neurodevelopmental disorders.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2024Review
- eIF2α phosphorylation evokes dystonia-like movements with D2-receptor and cholinergic origin and abnormal neuronal connectivity.bioRxiv : the preprint server for biology · 2024Article
- The integrated stress response pathway and neuromodulator signaling in the brain: lessons learned from dystonia.The Journal of clinical investigation · 2024Review
- The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation.Cell reports · 2024Article
- Article
- Is there a localized role for translational quality control?RNA (New York, N.Y.) · 2023Article
- Control of Selective mRNA Translation in Neuronal Subcellular Compartments in Health and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Remodeling the cellular stress response for enhanced genetic code expansion in mammalian cells.Nature communications · 2023Article
- Experimental upregulation of developmentally downregulated ribosomal protein large subunits 7 and 7A promotes axon regeneration after injury in vivo.Experimental neurology · 2023Article
- Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Local translation is rapidly regulated by extrinsic signals during neural wiring, but its control mechanisms remain elusive. Here we show that the extracellular cue Sema3A induces an initial burst in local translation that precisely controls phosphorylation of the translation initiation factor eIF2α via the unfolded protein response (UPR) kinase PERK. Strikingly, in contrast to canonical UPR signaling, Sema3A-induced eIF2α phosphorylation bypasses global translational repression and underlies an increase in local translation through differential activity of eIF2B mediated by protein phosphatase 1. Ultrasensitive proteomics analysis of axons reveals 75 proteins translationally controlled via the Sema3A-p-eIF2α pathway. These include proteostasis- and actin cytoskeleton-related proteins but not canonical stress markers. Finally, we show that PERK signaling is needed for directional axon migration and visual pathway development in vivo. Thus, our findings reveal a noncanonical eIF2 signaling pathway that controls selective changes in axon translation and is required for neural wiring.
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