Journal article
The deubiquitinase ataxin-3 requires Rad23 and DnaJ-1 for its neuroprotective role in Drosophila melanogaster
Neurobiology of disease, Vol.82, pp.12-21
10/01/2015
DOI: 10.1016/j.nbd.2015.05.010
PMCID: PMC4710962
PMID: 26007638
Abstract
Ataxin-3 is a deubiquitinase and polyglutamine (polyQ) disease protein with a protective role in Drosophila melanogaster models of neurodegeneration. In the fruit fly, wild-type ataxin-3 suppresses toxicity from several polyQ disease proteins, including a pathogenic version of itself that causes spinocerebellar ataxia type 3 and pathogenic huntingtin, which causes Huntington's disease. The molecular partners of ataxin-3 in this protective function are unclear. Here, we report that ataxin-3 requires its direct interaction with the ubiquitin-binding and proteasome-associated protein, Rad23 (known as hHR23A/B in mammals) in order to suppress toxicity from polyQ species in Drosophila. According to additional studies, ataxin-3 does not rely on autophagy or the proteasome to suppress polyQ-dependent toxicity in fly eyes. Instead this deubiquitinase, through its interaction with Rad23, leads to increased protein levels of the co-chaperone DnaJ-1 and depends on it to protect against degeneration. Through DnaJ-1, our data connect ataxin-3 and Rad23 to protective processes involved with protein folding rather than increased turnover of toxic polyQ species.
•Ataxin-3 is a deubiquitinase that suppresses neurodegeneration in Drosophila.•Ataxin-3 requires Rad23 and DnaJ-1 to protect against toxic species in flies.•Ataxin-3, through its interaction with Rad23, leads to increased levels of DnaJ-1.•DnaJ-1 requires stress-inducible heat shock proteins to suppress degeneration.
Details
- Title: Subtitle
- The deubiquitinase ataxin-3 requires Rad23 and DnaJ-1 for its neuroprotective role in Drosophila melanogaster
- Creators
- Wei-Ling Tsou - Wayne State UniversityMichelle Ouyang - Wayne State UniversityRyan R. Hosking - Wayne State UniversityJoanna R. Sutton - Wayne State UniversityJessica R. Blount - Wayne State UniversityAaron A. Burr - Wayne State UniversitySokol V. Todi - Wayne State University
- Resource Type
- Journal article
- Publication Details
- Neurobiology of disease, Vol.82, pp.12-21
- DOI
- 10.1016/j.nbd.2015.05.010
- PMID
- 26007638
- PMCID
- PMC4710962
- NLM abbreviation
- Neurobiol Dis
- ISSN
- 0969-9961
- eISSN
- 1095-953X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 10/01/2015
- Academic Unit
- Radiology
- Record Identifier
- 9984697722302771
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