PXD058788-1
PXD058788 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | A ubiquitin ligase protects lysosomes from CLN4 mutant-induced membrane damages |
| Description | Understanding how cells mitigate lysosomal damage is critical for unraveling pathogenic mechanisms of lysosome related diseases. Here we use organelle-specific proteomics in iPSC derived neurons (i3Neuron) and an in vitro lysosome damaging assay to demonstrate that lysosome damage, caused by the aggregation of Ceroid Lipofuscinosis Neuronal 4 (CLN4) linked DNAJC5 mutants on lysosomal membranes, serves as a critical pathogenic linchpin in CLN4 associated neurodegeneration. Intriguingly, in non neuronal cells, a ubiquitin dependent microautophagy mechanism downregulates CLN4 aggregates to counteract CLN4 associated lysotoxicity. Genome wide CRISPR screens identify the ubiquitin ligase CHIP as a central microautophagy regulator that confers ubiquitin dependent lysosome protection. Importantly, CHIP lysosome protection function is transferrable, as ectopic CHIP improves lysosomal function in CLN4 i3Neurons, and effectively alleviates lipofuscin accumulation and neurodegeneration in a Drosophila CLN4 disease model. Our study establishes CHIP mediated microautophagy as a key organelle damage guardian that preserves lysosome integrity, offering new insights into therapeutic development for CLN4 and other lysosome related neurodegenerative diseases. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-12-11 |
| AnnouncementXML | Submission_2024-12-11_13:54:17.650.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Ling Hao |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Carbamidomethyl; Oxidation; Acetyl |
| Instrument | Q Exactive HF-X |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-12-11 12:53:10 | ID requested | |
| ⏵ 1 | 2024-12-11 13:54:18 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: CHIP/STUB1, Ceroid Lipofuscinosis Neuronal/CLN4, lysosome membrane damage, autophagy/microautophagy, ubiquitin, lysosome storage disease/LSD, neurodegenerative disease, Drosophila disease model, DNAJC5/CSPalpha, DatasetType:Proteomics |
Contact List
| ling hao | |
|---|---|
| contact affiliation | University of Maryland |
| contact email | linghao1@umd.edu |
| lab head | |
| Ling Hao | |
| contact affiliation | University of Maryland |
| contact email | haolab.19@gmail.com |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/v07/MSV000096646/ |
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