PXD068255
PXD068255 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | TDP-43 skein-like inclusions formed by BAG3/HSP70 guided co-aggregation with actin binding proteins attached to actin filaments |
| Description | In multiple neurodegenerative diseases, the RNA binding protein TDP-43 forms cytoplasmic aggregates of distinct morphologies, including skein-like, spherical, diffuse, and granular inclusions. While the N-terminal self-oligomerization domain (NTD) regulates TDP-43 de-mixing into cytoplasmic droplets, inhibition of NTD-mediated oligomerization is shown here to promote the formation of skein-like inclusions. Utilizing proximity labeling/mass spectrometry, cellular stresses are shown to induce TDP-43 association with actin-binding proteins that include filamins and beta actinin. Small interfering RNA-mediated reduction of filamin in Drosophila ameliorates cell loss from cytoplasmic TDP-43, consistent with filamin/TDP-43 interaction enhancing cytotoxicity. TDP-43s association with actin-binding proteins is mediated by BAG3, a HSP70 family nucleotide exchange factor (NEF) that regulates proteostasis of actin-binding proteins. BAG2, another HSP70 NEF facilitates the formation of small, rounded TDP-43 inclusions. Our evidence demonstrates that both TDP-43 self-oligomerization and its binding partners, including HSP70 and the co-chaperones BAG2 and BAG3, drive formation of different types of TDP-43 inclusions. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-09-10 |
| AnnouncementXML | Submission_2025-09-10_07:36:39.445.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Jolene Diedrich |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-09-10 07:35:04 | ID requested | |
| ⏵ 1 | 2025-09-10 07:36:39 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: TDP43, DatasetType:Proteomics |
Contact List
| Don W. Cleveland | |
|---|---|
| contact affiliation | Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, Univ. of California |
| contact email | dcleveland@ucsd.edu |
| lab head | |
| Jolene Diedrich | |
| contact affiliation | SALK |
| contact email | jdiedrich@salk.edu |
| 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/v10/MSV000098098/ |
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