PXD031337-1

PXD031337 is an original dataset announced via ProteomeXchange.

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	2022-10-21
AnnouncementXML	Submission_2022-10-21_03:16:58.096.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MichaelGropp
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

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.

submitter keyword: Aggregation, Proteostasis, Oligomers, PolyQ, Huntington’s disease, Rnq1, Yeast, Neurodegeneration, Optogenetics, Prions

Prof. F. UlrichHartl
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
MichaelGropp
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

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://ftp.pride.ebi.ac.uk/pride/data/archive/2022/10/PXD031337

PRIDE project URI

• PRIDE
  1. PXD031337
     1. Label: PRIDE project
     2. Name: Formation of toxic oligomers of polyQ-expanded Huntingtin by prion-mediated cross-seeding