ArticleThe EMBO journal2022
Neuron-specific translational control shift ensures proteostatic resilience during ER stress.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Single cell RNA-sequencing reveals neuron type-specific vulnerabilities in a model of STXBP1-related disorder.Molecular psychiatry · 2026Article
- Loss of the endoplasmic reticulum protein canopy 1 disrupts the function and circuit organization of V2R-expressing vomeronasal sensory neurons.Development (Cambridge, England) · 2026Article
- Progressive Supranuclear Palsy PERK Haplotype B Selectively Translates DLX1 Promoting Tau Toxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Neurons with granulovacuolar degeneration bodies are resilient to tau-induced protein synthesis impairment.Science advances · 2026Article
- Astrocytic PERK Deficiency Drives Prefrontal Circuit Dysfunction and Depressive-Like Behaviors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- RIM and MUNC13 membrane-binding domains are essential for neuropeptide secretion.The Journal of cell biology · 2025Article
- Mitochondria-Nuclear Crosstalk: Orchestrating mtDNA Maintenance.Environmental and molecular mutagenesis · 2025Review
- Epigenetic suppression of creatine kinase B in adipocytes links endoplasmic reticulum stress to obesity-associated inflammation.Molecular metabolism · 2025Article
- Stearoyl-CoA desaturase-1: a potential therapeutic target for neurological disorders.Molecular neurodegeneration · 2024Review
- eIF2B localization and its regulation during the integrated stress response is cell-type specific.iScience · 2024Article
- The neuropathobiology of multiple sclerosis.Nature reviews. Neuroscience · 2024Review
- Neuron-to-astrocyte proteostatic stress signaling in response to tau pathology.Neural regeneration research · 2024Article
- Pharmacologic activation of a compensatory integrated stress response kinase promotes mitochondrial remodeling in PERK-deficient cells.Cell chemical biology · 2023Article
- Article
- Pharmacologic Activation of a Compensatory Integrated Stress Response Kinase Promotes Mitochondrial Remodeling in PERK-deficient Cells.bioRxiv : the preprint server for biology · 2023Article
- Intraneuronal tau aggregation induces the integrated stress response in astrocytes.Journal of molecular cell biology · 2023Article
- Signaling plasticity in the integrated stress response.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteostasis is essential for cellular survival and particularly important for highly specialised post-mitotic cells such as neurons. Transient reduction in protein synthesis by protein kinase R-like endoplasmic reticulum (ER) kinase (PERK)-mediated phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α) is a major proteostatic survival response during ER stress. Paradoxically, neurons are remarkably tolerant to PERK dysfunction, which suggests the existence of cell type-specific mechanisms that secure proteostatic stress resilience. Here, we demonstrate that PERK-deficient neurons, unlike other cell types, fully retain the capacity to control translation during ER stress. We observe rescaling of the ATF4 response, while the reduction in protein synthesis is fully retained. We identify two molecular pathways that jointly drive translational control in PERK-deficient neurons. Haem-regulated inhibitor (HRI) mediates p-eIF2α and the ATF4 response and is complemented by the tRNA cleaving RNase angiogenin (ANG) to reduce protein synthesis. Overall, our study elucidates an intricate back-up mechanism to ascertain translational control during ER stress in neurons that provides a mechanistic explanation for the thus far unresolved observation of neuronal resilience to proteostatic stress.
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