ArticleThe Journal of cell biology2022
CHMP2B regulates TDP-43 phosphorylation and cytotoxicity independent of autophagy via CK1.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- Embedded CRISPRi Enhances Gene-Silencing Efficiency in Drosophila.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification of novel protein markers and therapeutic targets for common urological cancers by integrating large-scale human plasma proteome with the genome.Scientific reports · 2026Article
- ESCRT-III function in membrane fission and repair.Nature reviews. Molecular cell biology · 2026Review
- Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.Molecular neurobiology · 2025Review
- Article
- Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration.Molecular neurodegeneration · 2025Review
- Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.Translational neurodegeneration · 2025Review
- Identification of autophagy-related immune targets for enhancing immunotherapy in pancreatic cancer aggressiveness.Discover oncology · 2025Article
- Molecular mechanism on autophagy associated cardiovascular dysfunction inFrontiers in cell and developmental biology · 2025Review
- CHMP2B promotes CHMP7 mediated nuclear pore complex injury in sporadic ALS.Acta neuropathologica communications · 2024Article
- Nuclear and degradative functions of the ESCRT-III pathway: implications for neurodegenerative disease.Nucleus (Austin, Tex.) · 2024Review
- Nuclear pore complex and nucleocytoplasmic transport disruption in neurodegeneration.FEBS letters · 2023Review
- A Novel Drosophila-based Drug Repurposing Platform Identified Fingolimod As a Potential Therapeutic for TDP-43 Proteinopathy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Transactive response DNA-binding protein 43 is enriched at the centrosome in human cells.Brain : a journal of neurology · 2023Article
- FTD/ALS Type 7-Associated Thr104Asn Mutation of CHMP2B Blunts Neuronal Process Elongation, and Is Recovered by Knockdown of Arf4, the Golgi Stress Regulator.Neurology international · 2023Article
- Review
- Inhibition of the MEK/ERK pathway suppresses immune overactivation and mitigates TDP-43 toxicity in a Drosophila model of ALS.Immunity & ageing : I & A · 2023Article
- Looking for answers far away from the soma-the (un)known axonal functions of TDP-43, and their contribution to early NMJ disruption in ALS.Molecular neurodegeneration · 2023Review
- Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder.Biomedicines · 2023Review
- Roles of Pyroptosis-Related Genes in the Diagnosis and Subtype Classification of Periodontitis.Journal of immunology research · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ESCRT protein CHMP2B and the RNA-binding protein TDP-43 are both associated with ALS and FTD. The pathogenicity of CHMP2B has mainly been considered a consequence of autophagy-endolysosomal dysfunction, whereas protein inclusions containing phosphorylated TDP-43 are a pathological hallmark of ALS and FTD. Intriguingly, TDP-43 pathology has not been associated with the FTD-causing CHMP2BIntron5 mutation. In this study, we identify CHMP2B as a modifier of TDP-43-mediated neurodegeneration in a Drosophila screen. Down-regulation of CHMP2B reduces TDP-43 phosphorylation and toxicity in flies and mammalian cells. Surprisingly, although CHMP2BIntron5 causes dramatic autophagy dysfunction, disturbance of autophagy does not alter TDP-43 phosphorylation levels. Instead, we find that inhibition of CK1, but not TTBK1/2 (all of which are kinases phosphorylating TDP-43), abolishes the modifying effect of CHMP2B on TDP-43 phosphorylation. Finally, we uncover that CHMP2B modulates CK1 protein levels by negatively regulating ubiquitination and the proteasome-mediated turnover of CK1. Together, our findings propose an autophagy-independent role and mechanism of CHMP2B in regulating CK1 abundance and TDP-43 phosphorylation.
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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.