Nature Cell Biology
4, 826 - 831 (2002)
Published online: 30 September 2002; | doi:10.1038/ncb863
Polyglutamine protein aggregates are dynamicSoojin Kim1, Ellen A. A. Nollen1, Kazunori Kitagawa2, Vytautas P. Bindokas3
& Richard I. Morimoto11
Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208 USA
2
Department of Molecular Pathology, Osaka University Medical School, Suita, Osaka 565, Japan
3
Department of Neurobiology, Pharmacology, and Physiology, The University of Chicago, Chicago, IL 60537, USA
Correspondence should be addressed to Richard I. Morimoto r-morimoto@northwestern.eduProtein 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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