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PXD031337-1

PXD031337 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFormation of toxic oligomers of polyQ-expanded Huntingtin by prion-mediated cross-seeding
DescriptionManifestation 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.
HostingRepositoryPRIDE
AnnounceDate2022-10-21
AnnouncementXMLSubmission_2022-10-21_03:16:58.096.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMichaelGropp
SpeciesList scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-01-30 14:03:03ID requested
12022-10-21 03:16:58announced
22023-11-14 08:54:48announced2023-11-14: Updated project metadata.
Publication List
Keyword List
submitter keyword: Aggregation, Proteostasis, Oligomers, PolyQ, Huntington’s disease, Rnq1, Yeast, Neurodegeneration, Optogenetics, Prions
Contact List
Prof. F. UlrichHartl
contact affiliationDepartment of Cellular Biochemistry, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
contact emailuhartl@biochem.mpg.de
lab head
MichaelGropp
contact affiliationDepartment of Cellular Biochemistry, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
contact emailmgropp@biochem.mpg.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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