Open Close
Reference
Citation
Nezis, I.P., Simonsen, A., Sagona, A.P., Finley, K., Gaumer, S., Contamine, D., Rusten, T.E., Stenmark, H., Brech, A. (2008). Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain.  J. Cell Biol. 180(6): 1065--1071.
FlyBase ID
FBrf0204151
Publication Type
Research paper
Abstract

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.

PubMed ID
PubMed Central ID
PMC2290837 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell Biol.
    Title
    Journal of Cell Biology
    Publication Year
    1966-
    ISBN/ISSN
    0021-9525
    Data From Reference