PXD009760

PXD009760 is an original dataset announced via ProteomeXchange.

Title	A complex of C9ORF72 and p62 uses arginine methylation to eliminate stress granules by autophagy - PART 3
Description	Mutations in proteins like FUS which cause Amyotrophic Lateral Sclerosis (ALS) result in the aberrant formation of stress granules while ALS-linked mutations in other proteins impede elimination of stress granules. Repeat expansions in C9ORF72, the major cause of ALS, reduce C9ORF72 levels but how this impacts stress granules is uncertain. Here, we demonstrate that C9ORF72 associates with the autophagy receptor p62 and controls elimination of stress granules by autophagy. This requires p62 to associate via the Tudor protein SMN with proteins, including FUS, that are symmetrically arginine-methylated by PRMT5. Mice lacking p62 accumulate arginine-methylated proteins and alterations in FUS-dependent splicing. Finally, patients with C9ORF72 repeat expansions accumulate symmetric arginine dimethylated proteins which co-localize with p62. This suggests that C9ORF72 initiates a cascade of ALS-linked proteins (C9ORF72, p62, SMN, FUS) to recognize stress granules for degradation by autophagy and hallmarks of a defect in this process are observable in ALS patients.
HostingRepository	PRIDE
AnnounceDate	2018-07-25
AnnouncementXML	Submission_2018-07-25_03:42:44.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maneka Chitiprolu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	asymmetric dimethyl-L-arginine; symmetric dimethyl-L-arginine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-11 06:00:03	ID requested
⏵ 1	2018-07-25 03:42:45	announced

Dataset with its publication pending

curator keyword: Biological

submitter keyword: FUS, PRMT5, Arginine Dimethylation, Oxidate Stress, ALS, LC-MSMS

Derrick Gibbings
contact affiliation	Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5
contact email	gibbings@uottawa.ca
lab head
Maneka Chitiprolu
contact affiliation	University of Ottawa
contact email	mchit103@uottawa.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009760
     1. Label: PRIDE project
     2. Name: A complex of C9ORF72 and p62 uses arginine methylation to eliminate stress granules by autophagy - PART 3