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- Title
Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state.
- Authors
Kitamura, Akira; Kubota, Hiroshi; Pack, Chan-Gi; Matsumoto, Gen; Hirayama, Shoshiro; Takahashi, Yasuo; Kimura, Hiroshi; Kinjo, Masataka; Morimoto, Richard I.; Nagata, Kazuhiro
- Abstract
Polyglutamine (polyQ)-expansion proteins cause neurodegenerative disorders including Huntington's disease, Kennedy's disease and various ataxias. The cytotoxicity of these proteins is associated with the formation of aggregates or other conformationally toxic species. Here, we show that the cytosolic chaperonin CCT (also known as TRiC) can alter the course of aggregation and cytotoxicity of huntingtin (Htt)–polyQ proteins in mammalian cells. Disruption of the CCT complex by RNAi-mediated knockdown enhanced Htt–polyQ aggregate formation and cellular toxicity. Analysis of the aggregation states of the Htt–polyQ proteins by fluorescence correlation spectroscopy revealed that CCT depletion results in the appearance of soluble Htt–polyQ aggregates. Similarly, overexpression of all eight subunits of CCT suppressed Htt aggregation and neuronal cell death. These results indicate that CCT has an essential role in protecting against the cytotoxicity of polyQ proteins by affecting the course of aggregation.
- Subjects
CYTOSOL; MOLECULAR chaperones; GLUTAMINE; CELL-mediated cytotoxicity; CELL aggregation; HUNTINGTON disease; NEURODEGENERATION
- Publication
Nature Cell Biology, 2006, Vol 8, Issue 10, p1163
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb1478