Polyglutamine protein aggregates are dynamicKim, S., Nollen, E. A. A., Kitagawa, K., Bindokas, V. P. & Morimoto, R. I., 2002, In : Nature Cell Biology. 4, 10, p. 826-831 6 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||6|
|Journal||Nature Cell Biology|
|Publication status||Published - 2002|
- Animals, Bacterial Proteins, Cell Compartmentation, Eukaryotic Cells, Fluorescence Recovery After Photobleaching, Green Fluorescent Proteins, HSP70 Heat-Shock Proteins, HeLa Cells, Humans, Inclusion Bodies, Luminescent Proteins, Macromolecular Substances, Molecular Chaperones, Neurodegenerative Diseases, Peptides, Protein Folding, Recombinant Fusion Proteins, TATA-Box Binding Protein, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.