Polyglutamine protein aggregates are dynamic

Soojin Kim, Ellen A.A. Nollen, Kazunori Kitagawa, Vytautas P. Bindokas, Richard I Morimoto

Research output: Contribution to journalArticle

236 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)826-830
Number of pages5
JournalNature Cell Biology
Volume4
Issue number10
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Polyglutamine protein aggregates are dynamic'. Together they form a unique fingerprint.

  • Cite this

    Kim, S., Nollen, E. A. A., Kitagawa, K., Bindokas, V. P., & Morimoto, R. I. (2002). Polyglutamine protein aggregates are dynamic. Nature Cell Biology, 4(10), 826-830. https://doi.org/10.1038/ncb863