RRC ID |
34903
|
著者 |
Vinatier G, Corsi JM, Mignotte B, Gaumer S.
|
タイトル |
Quantification of Ataxin-3 and Ataxin-7 aggregates formed in vivo in Drosophila reveals a threshold of aggregated polyglutamine proteins associated with cellular toxicity.
|
ジャーナル |
Biochem Biophys Res Commun
|
Abstract |
Polyglutamine diseases are nine dominantly inherited neurodegenerative pathologies caused by the expansion of a polyglutamine domain in a protein responsible for the disease. This expansion leads to protein aggregation, inclusion formation and toxicity. Despite numerous studies focusing on the subject, whether soluble polyglutamine proteins are responsible for toxicity or not remains debated. To focus on this matter, we evaluated the level of soluble and insoluble truncated pathological Ataxin-3 in vivo in Drosophila, in presence or absence of two suppressors (i.e. Hsp70 and non-pathological Ataxin-3) and along aging. Suppressing truncated Ataxin-3-induced toxicity resulted in a lowered level of aggregated polyglutamine protein. Interestingly, aggregates accumulated as flies aged and reached a maximum level when cell death was detected. Our results were similar with two other pathological polyglutamine proteins, namely truncated Ataxin-7 and full-length Ataxin-3. Our data suggest that accumulation of insoluble aggregates beyond a critical threshold could be responsible for toxicity.
|
巻・号 |
464(4)
|
ページ |
1060-1065
|
公開日 |
2015-9-4
|
DOI |
10.1016/j.bbrc.2015.07.071
|
PII |
S0006-291X(15)30301-6
|
PMID |
26210447
|
MeSH |
Aging / genetics
Aging / metabolism
Aging / pathology
Animals
Animals, Genetically Modified
Ataxin-3 / chemistry*
Ataxin-3 / genetics
Ataxin-3 / metabolism*
Ataxin-7 / chemistry*
Ataxin-7 / genetics
Ataxin-7 / metabolism*
Disease Models, Animal
Drosophila melanogaster / genetics
Drosophila melanogaster / metabolism
Female
Heredodegenerative Disorders, Nervous System / genetics
Heredodegenerative Disorders, Nervous System / metabolism
Heredodegenerative Disorders, Nervous System / pathology
Humans
Male
Models, Neurological
Mutant Proteins / chemistry
Mutant Proteins / genetics
Mutant Proteins / metabolism
Peptides / chemistry
Peptides / genetics
Peptides / metabolism
Protein Aggregates
Protein Aggregation, Pathological / genetics
Protein Aggregation, Pathological / metabolism*
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Repressor Proteins / chemistry*
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Solubility
|
IF |
2.985
|
引用数 |
0
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
BIOPHYSICS
|
リソース情報 |
ショウジョウバエ |
5680R-2 |