A C-terminal ataxin-2 disordered region promotes Huntingtin protein aggregation and neurodegeneration in Drosophila models of Huntington's disease.
Drosophila
Ataxin-2
Htt
RNP granule
neurodegeneration
Journal
G3 (Bethesda, Md.)
ISSN: 2160-1836
Titre abrégé: G3 (Bethesda)
Pays: England
ID NLM: 101566598
Informations de publication
Date de publication:
08 12 2021
08 12 2021
Historique:
received:
08
09
2021
accepted:
01
10
2021
pubmed:
1
11
2021
medline:
8
1
2022
entrez:
31
10
2021
Statut:
ppublish
Résumé
The Ataxin-2 (Atx2) protein contributes to the progression of neurodegenerative phenotypes in animal models of amyotrophic lateral sclerosis (ALS), type 2 spinocerebellar ataxia (SCA-2), Parkinson's disease, and Huntington's disease (HD). However, because the Atx2 protein contains multiple separable activities, deeper understanding requires experiments to address the exact mechanisms by which Atx2 modulates neurodegeneration (ND) progression. Recent work on two ALS models, C9ORF72 and FUS, in Drosophila has shown that a C-terminal intrinsically disordered region (cIDR) of Atx2 protein, required for assembly of ribonucleoprotein (RNP) granules, is essential for the progression of neurodegenerative phenotypes as well as for accumulation of protein inclusions associated with these ALS models. Here, we show that the Atx2-cIDR also similarly contributes to the progression of degenerative phenotypes and accumulation of Huntingtin protein aggregates in Drosophila models of HD. Because Huntingtin is not an established component of RNP granules, these observations support a recently hypothesized, unexpected protein-handling function for RNP granules, which could contribute to the progression of Huntington's disease and, potentially, other proteinopathies.
Identifiants
pubmed: 34718534
pii: 6385240
doi: 10.1093/g3journal/jkab355
pmc: PMC8664476
pii:
doi:
Substances chimiques
Ataxin-2
0
Ataxins
0
Drosophila Proteins
0
Huntingtin Protein
0
Protein Aggregates
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.
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