A complex of C9ORF72 and p62 uses arginine methylation to eliminate stress granules by autophagy

Maneka Chitiprolu, Chantal Jagow, Veronique Tremblay, Emma Bondy-Chorney, Geneviève Paris, Alexandre Savard, Gareth Palidwor, Francesca A. Barry, Lorne Zinman, Julia Keith, Ekaterina Rogaeva, Janice Robertson, Mathieu Lavallée-Adam, John Woulfe, Jean-François Couture, Jocelyn Côté and Derrick Gibbings ()
Additional contact information
Maneka Chitiprolu: University of Ottawa
Chantal Jagow: University of Ottawa
Veronique Tremblay: University of Ottawa
Emma Bondy-Chorney: University of Ottawa
Geneviève Paris: University of Ottawa
Alexandre Savard: University of Ottawa
Gareth Palidwor: Ottawa Hospital Research Institute
Francesca A. Barry: University of Ottawa
Lorne Zinman: Sunnybrook Health Sciences Centre
Julia Keith: Sunnybrook Health Sciences Centre
Ekaterina Rogaeva: University of Toronto
Janice Robertson: University of Toronto
Mathieu Lavallée-Adam: University of Ottawa
John Woulfe: University of Ottawa
Jean-François Couture: University of Ottawa
Jocelyn Côté: University of Ottawa
Derrick Gibbings: University of Ottawa

Nature Communications, 2018, vol. 9, issue 1, 1-18

Abstract: Abstract 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 methylated on arginines. Mice lacking p62 accumulate arginine-methylated proteins and alterations in FUS-dependent splicing. 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-05273-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05273-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-05273-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().