Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain
Open accessAbstract
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.
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Ref(2)P is the Drosophila homolog of P62 and can selectively target ubiquitinated proteins for autophagic degradation.
“we introduced Ref(2)P, the Drosophila homolog of P62 [23], which can selectively target ubiquitinated proteins for autophagical degradation [24]”
From Overexpression of pink1 or parkin in indirect flight muscles promotes mitochondrial proteostasis and extends lifespan in Drosophila melanogaster (2019) · cites this paper as [23]
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- Authors
- Nezis, I. P., Simonsen, A., Sagona, A. P., Finley, K., Gaumer, S., Contamine, D., Rusten, T. E., Stenmark, H., & Brech, A.
- Affiliations
- University of Oslo (NO)
- Salk Institute for Biological Studies (US)
- 3Université Versailles St-Quentin, Laboratoire de Génétique et de Biologie Cellulaire, Versailles Cedex 78035, France
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2008-03-17
- Volume
- 180
- Issue
- 6
- Pages
- 1065-1071
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2290837
- OpenAlex
- W2135686999
- Cited by
- 370
- References
- 23
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 14 · 2023: 28 · 2022: 24 · 2021: 27 · 2020: 17 · 2019: 28 · 2018: 26 · 2017: 16 · 2016: 27 · 2015: 13 · 2014: 23 · 2013: 14 · 2012: 24
- FWCI
- 15.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- p62, Drosophila melanogaster, protein aggregation, ubiquitin, autophagy, Atg8a, proteasome, neurodegenerative disease models, protein turnover, ubiquitin-binding domain
- MeSH terms
- Sequestosome-1 Protein, Aging, Animals, Autophagy, Brain, Inclusion Bodies, DNA-Binding Proteins, Drosophila melanogaster, Humans, Mutation, Nerve Tissue Proteins, Nuclear Proteins, Protein Structure, Tertiary, Neurodegenerative Diseases, Ubiquitin, Drosophila Proteins, Proteasome Endopeptidase Complex, Adaptor Proteins, Signal Transducing, Ubiquitination
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