ArticleNature structural & molecular biology2017
A mammalian nervous-system-specific plasma membrane proteasome complex that modulates neuronal function.
Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Proteasome mutations associated with CANDLE syndrome cause altered neuronal development by dysregulating polyamine synthesis.The Journal of clinical investigation · 2026Article
- An unexpected molecular explanation for how tau aggregation begins in Alzheimer's disease.Nature neuroscience · 2026Article
- Neuroproteasomes regulate endogenous tau paired helical filament formation in an APOE genotype- and age-dependent manner.Nature neuroscience · 2026Article
- Dendritic translation and neuroproteasome-mediated degradation of endogenous tau revealed by STARFISH.Nature neuroscience · 2026Article
- Article
- Plasticity in the structure and assembly of proteasomes.The Journal of biological chemistry · 2026Review
- Proteomic and transcriptomic signatures of cytoskeletal remodeling during morphogenesis in the basal metazoanFrontiers in cell and developmental biology · 2026Article
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- Tuning insulin receptor signaling using de novo-designed agonists.Molecular cell · 2025Article
- A chaperone-proteasome-based fragmentation machinery is essential for aggrephagy.Nature cell biology · 2025Article
- Proteasome-derived peptides: separating the trash from the recycling.Trends in biochemical sciences · 2025Review
- Compartmentalization of proteasomes in lipid rafts and exosomes: unveiling molecular interactions in vaping-related cellular processes.Archives of toxicology · 2025Article
- Neurodegeneration models in Parkinson's disease: cellular and molecular paths to neuron death.Behavioral and brain functions : BBF · 2025Review
- Regulation of translation elongation and integrated stress response in heat-shocked neurons.Cell reports · 2025Article
- Immunoproteasome Inhibition Impairs Differentiation but Not Survival of T Helper 17 Cells.Cells · 2025Article
- Protocol to study neuronal membrane proteasome function in mouse peripheral sensory neurons.STAR protocols · 2025Article
- Autoantibodies in the Pathogenesis of Podocytopathies.Journal of the American Society of Nephrology : JASN · 2025Article
- Tracking proteasome degradation: A cross-organ analysis via intact degradomics mass spectrometry.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- β-Amyloid impairs Proteasome structure and function. Proteasome activation mitigates amyloid induced toxicity and cognitive deficits.bioRxiv : the preprint server for biology · 2025Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
In the nervous system, rapidly occurring processes such as neuronal transmission and calcium signaling are affected by short-term inhibition of proteasome function. It is unclear how proteasomes are able to acutely regulate such processes, as this action is inconsistent with their canonical role in proteostasis. Here we describe a mammalian nervous-system-specific membrane proteasome complex that directly and rapidly modulates neuronal function by degrading intracellular proteins into extracellular peptides that can stimulate neuronal signaling. This proteasome complex is closely associated with neuronal plasma membranes, exposed to the extracellular space, and catalytically active. Selective inhibition of the membrane proteasome complex by a cell-impermeable proteasome inhibitor blocked the production of extracellular peptides and attenuated neuronal-activity-induced calcium signaling. Moreover, we observed that membrane-proteasome-derived peptides were sufficient to induce neuronal calcium signaling. Our discoveries challenge the prevailing notion that proteasomes function primarily to maintain proteostasis, and highlight a form of neuronal communication that takes place through a membrane proteasome complex.
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Registered trials
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.