Polyglutamine protein aggregates are dynamic

被引:243
作者
Kim, S [1 ]
Nollen, EAA
Kitagawa, K
Bindokas, VP
Morimoto, RI
机构
[1] Northwestern Univ, Rice Inst Biomed Res, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA
[2] Osaka Univ, Sch Med, Dept Mol Pathol, Suita, Osaka 565, Japan
[3] Univ Chicago, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60537 USA
关键词
D O I
10.1038/ncb863
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Protein aggregation and the formation of inclusion bodies are hallmarks of the cytopathology of neurodegenerative diseases, including Huntington's disease, Amyotropic lateral sclerosis, Parkinson's disease and Alzheimer's disease. The cellular toxicity associated with protein aggregates has been suggested to result from the sequestration of essential proteins that are involved in key cellular events, such as transcription, maintenance of cell shape and motility, protein folding and protein degradation. Here, we use fluorescence imaging of living cells to show that polyglutamine protein aggregates are dynamic structures in which glutamine-rich proteins are tightly associated, but which exhibit distinct biophysical interactions. In contrast, the interaction between wild-type, but not mutant, Hsp70 exhibits rapid kinetics of association and dissociation similar to interactions between Hsp70 and thermally unfolded substrates. These studies provide new insights into the composite organization and formation of protein aggregates and show that molecular chaperones are not sequestered into aggregates, but are instead transiently associated.
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收藏
页码:826 / 831
页数:6
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