⮝ Full datasets listing
PXD071655
PXD071655 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis |
| Description | Aggregation of the protein tau defines tauopathies, the most common age-related neurodegenerative diseases, which include Alzheimers disease and frontotemporal dementia. Specific neuronal subtypes are selectively vulnerable to tau aggregation, subsequent dysfunction, and death. However, molecular mechanisms underlying cell type-selective vulnerability are unknown. To systematically uncover the cellular factors controlling the accumulation of tau aggregates in human neurons, we conducted a genome-wide CRISPRi screen in iPSC-derived neurons. The screen uncovered both known and unexpected pathways, including UFMylation and GPI anchor biosynthesis, that control tau oligomer levels. We discovered that the E3 ubiquitin ligase CUL5SOCS4 controls tau levels in human neurons, ubiquitinates tau, and is correlated with resilience to tauopathies in human disease. Disruption of mitochondrial function promotes proteasomal misprocessing of tau, generating disease-relevant tau proteolytic fragments and changes tau aggregation in vitro. These results systematically reveal principles of tau proteostasis in human neurons and suggest potential therapeutic targets for tauopathies. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-12-05 |
| AnnouncementXML | Submission_2025-12-05_15:55:08.641.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Justin M McKetney |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Phospho; Acetyl; Oxidation |
| Instrument | Orbitrap Exploris 480; Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-12-05 15:07:54 | ID requested | |
| ⏵ 1 | 2025-12-05 15:55:09 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: CRISPR, Neurons, Tau protein, Neurodegeneration, Proteostasis, CUL5, Ubiquitination, Aggregation, Proteasome, DatasetType:Proteomics |
Contact List
| Martin Kampmann | |
|---|---|
| contact affiliation | University of California San Francisco |
| contact email | martin.kampmann@ucsf.edu |
| lab head | |
| Danielle Swaney | |
| contact affiliation | UCSF |
| contact email | danielle.swaney@gladstone.ucsf.edu |
| lab head | |
| Justin M McKetney | |
| contact affiliation | UCSF |
| contact email | justinmcketney@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-ftp.ucsd.edu/v11/MSV000100129/ |
