RRC ID 34903
Author Vinatier G, Corsi JM, Mignotte B, Gaumer S.
Title Quantification of Ataxin-3 and Ataxin-7 aggregates formed in vivo in Drosophila reveals a threshold of aggregated polyglutamine proteins associated with cellular toxicity.
Journal 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.
Volume 464(4)
Pages 1060-1065
Published 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 2.705
Times Cited 0
Drosophila 5680R-2