PXD017330

PXD017330 is an original dataset announced via ProteomeXchange.

Title	Spatio-temporal Proteomic Analysis of Stress Granule disassembly using APEX Reveals Regulation by SUMOylation and links to ALS pathogenesis
Description	Cytoplasmic stress granules (SG) are membraneless organelles that form in response to a variety of cellular stresses by phase-separation of proteins associated with non-translating mRNAs. SG have recently been linked with neurodegeneration, including ALS, however there has been no systematic investigation of SG composition in normal and disease contexts. We created a proximity proteomics platform by using multiple ascorbate peroxidase (APEX2) baits to comprehensively characterize the spatio-temporal organization of SG in normal and disease (ALS-like) conditions. Multi-bait APEX enhanced sensitivity and enabled cross-validation, leading to the mass spectrometric discovery of 109 additional SG proteins, and internal SG substructures at proteomic resolution. A proteomic analysis of SG disassembly over time revealed a group of 349 proteins recruited specifically during SG disassembly, which we named disassembly-engaged proteins (DEPs), including SUMO ligases. A parallel study of SG disassembly in the presence of C9ORF72-associated dipeptides, which are found in patients with ALS and frontotemporal dementia revealed impaired SG disassembly and DEP recruitment, which may be linked to neurodegeneration. Finally, broad SUMOylation of SG proteins was required for SG disassembly, and impaired by C9ORF72-associated dipeptides. Altogether, our study provides a valuable resource, and dissects the SG spatio-temporal proteomic landscape, revealing basic and disease-relevant mechanisms of SG dynamics.
HostingRepository	PRIDE
AnnounceDate	2020-10-19
AnnouncementXML	Submission_2020-10-18_23:13:09.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Geiger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-30 01:17:44	ID requested
⏵ 1	2020-10-18 23:13:10	announced

Dataset with its publication pending

submitter keyword: Stress granules, APEX, Proteomics, SUMOylation

Professor Tamar Geiger
contact affiliation	Dept. of Human Molecular Genetics and Biochemistry Sackler Faculty of Medicine Tel Aviv University Israel
contact email	geiger@tauex.tau.ac.il
lab head
Tamar Geiger
contact affiliation	Tel Aviv University
contact email	geiger@tauex.tau.ac.il
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/2020/10/PXD017330

PRIDE project URI

• PRIDE
  1. PXD017330
     1. Label: PRIDE project
     2. Name: Spatio-temporal Proteomic Analysis of Stress Granule disassembly using APEX Reveals Regulation by SUMOylation and links to ALS pathogenesis