| Title: |
Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain |
| Authors: |
Nezis, Ioannis P.; Simonsen, Anne; Sagona, Antonia P.; Finley, Kim; Gaumer, Sébastien; Contamine, Didier; Rusten, Tor Erik; Stenmark, Harald; Brech, Andreas |
| Source: |
The Journal of Cell Biology ; volume 180, issue 6, page 1065-1071 ; ISSN 1540-8140 0021-9525 |
| Publisher Information: |
Rockefeller University Press |
| Publication Year: |
2008 |
| Description: |
p62 has been proposed to mark ubiquitinated protein bodies for autophagic degradation. We report that the Drosophila melanogaster p62 orthologue, Ref(2)P, is a regulator of protein aggregation in the adult brain. We demonstrate that Ref(2)P localizes to age-induced protein aggregates as well as to aggregates caused by reduced autophagic or proteasomal activity. A similar localization to protein aggregates is also observed in D. melanogaster models of human neurodegenerative diseases. Although atg8a autophagy mutant flies show accumulation of ubiquitin- and Ref(2)P-positive protein aggregates, this is abrogated in atg8a/ref(2)P double mutants. Both the multimerization and ubiquitin binding domains of Ref(2)P are required for aggregate formation in vivo. Our findings reveal a major role for Ref(2)P in the formation of ubiquitin-positive protein aggregates both under physiological conditions and when normal protein turnover is inhibited. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1083/jcb.200711108 |
| Availability: |
https://doi.org/10.1083/jcb.200711108; https://rupress.org/jcb/article-pdf/180/6/1065/1570947/jcb_200711108.pdf |
| Accession Number: |
edsbas.89804AED |
| Database: |
BASE |