PXD018505

PXD018505 is an original dataset announced via ProteomeXchange.

Title	Inclusion bodies formed by polyglutamine and poly(glycine-alanine) are enriched with distinct proteomes but converge in proteins that are risk factors for disease and involved in protein degradation
Description	Poly(glycine-alanine) (polyGA) is one of the dipolypeptides expressed in Motor Neuron Disease caused by C9ORF72 mutations and accumulates as inclusion bodies in the brain of patients. Superficially these inclusions are similar to those formed by polyglutamine (polyQ) in Huntington’s disease and both have been reported to form an amyloid-like structure suggesting they might aggregate via similar mechanisms to confer cellular dysfunction similarly. Here we investigated which endogenous proteins were enriched in these inclusions and whether aggregation-prone lengths of polyQ (Q97), in context of Huntingtin exon 1, shared similar patterns to aggregation-prone lengths of polyGA (101GA). When co-expressed in the same cell, polyGA101 and HttQ97 inclusions adopted distinct phases with no overlap suggesting different endogenous proteins would be enriched. Proteomic analyses indeed yielded distinct sets of endogenous proteins recruited into the inclusion types. The proteosome, microtubules, Tric chaperones, and translational machinery were enriched in polyGA aggregates, whereas Dnaj chaperones, nuclear envelope and RNA splicing proteins were enriched in polyQ aggregates. Both structures revealed a synergy of degradation machinery including proteins in the polyQ aggregates that are risk factors for other neurodegenerative diseases involving protein aggregation when mutated, which suggests a convergence point in the pathomechanisms of these diseases.
HostingRepository	PRIDE
AnnounceDate	2020-08-18
AnnouncementXML	Submission_2020-09-04_04:43:20.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mona Radwan
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-14 01:52:16	ID requested
1	2020-08-18 03:57:00	announced
⏵ 2	2020-09-04 04:43:21	announced	2020-09-04: Updated publication reference for PubMed record(s): 32857759.

Radwan M, Lilley JD, Ang CS, Reid GE, Hatters DM, Immiscible inclusion bodies formed by polyglutamine and poly(glycine-alanine) are enriched with distinct proteomes but converge in proteins that are risk factors for disease and involved in protein degradation. PLoS One, 15(8):e0233247(2020) [pubmed]

submitter keyword: inclusions, C9ORF72, Huntington, proteosome, Chaperones

Prof. Danny M. Hatters
contact affiliation	NHMRC Senior Research Fellow Department of Biochemistry and Molecular Biology | Faculty of Medicine, Dentistry and Health Sciences Level 2 South, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Road The University of Melbourne, Victoria 3010 Australia
contact email	dhatters@unimelb.edu.au
lab head
Mona Radwan
contact affiliation	PhD student
contact email	monar@student.unimelb.edu.au
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/2020/08/PXD018505

PRIDE project URI

• PRIDE
  1. PXD018505
     1. Label: PRIDE project
     2. Name: Inclusion bodies formed by polyglutamine and poly(glycine-alanine) are enriched with distinct proteomes but converge in proteins that are risk factors for disease and involved in protein degradation