PXD031337 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Formation of toxic oligomers of polyQ-expanded Huntingtin by prion-mediated cross-seeding |
Description | Manifestation of aggregate pathology in Huntington’s disease is thought to be facilitated by a preferential vulnerability of affected brain cells to age-dependent proteostatic decline. To understand how specific cellular backgrounds may facilitate pathologic aggregation, we utilized the yeast model in which polyQ-expanded Huntingtin forms aggregates only when the endogenous prion-forming protein Rnq1 is in its amyloid-like prion [PIN+] conformation. We employed optogenetic clustering of polyQ protein as an orthogonal method to induce polyQ aggregation in prion-free [pin-] cells. Optogenetic aggregation circumvented the prion requirement for the formation of detergent-resistant polyQ inclusions, but bypassed the formation of toxic polyQ oligomers, which accumulated specifically in [PIN+] cells. Reconstitution of aggregation in vitro suggested that these polyQ oligomers formed through direct templating on Rnq1 prions. These findings shed light on the mechanism of prion-mediated formation of oligomers, which may play a role in triggering polyQ pathology in the patient brain. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:54:47.964.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Michael Gropp |
SpeciesList | scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-01-30 14:03:03 | ID requested | |
1 | 2022-10-21 03:16:58 | announced | |
⏵ 2 | 2023-11-14 08:54:48 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Aggregation, Proteostasis, Oligomers, PolyQ, Huntington’s disease, Rnq1, Yeast, Neurodegeneration, Optogenetics, Prions |
Contact List
Prof. F. Ulrich Hartl |
contact affiliation | Department of Cellular Biochemistry, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany |
contact email | uhartl@biochem.mpg.de |
lab head | |
Michael Gropp |
contact affiliation | Department of Cellular Biochemistry, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany |
contact email | mgropp@biochem.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD031337
- Label: PRIDE project
- Name: Formation of toxic oligomers of polyQ-expanded Huntingtin by prion-mediated cross-seeding