Aggregate-centered redistribution of proteins by mutant huntingtin
详细信息 查看全文
- 作者：Leigh Anne Swayne ; Janice E.A. Braun
- 关键词：Huntingtin ; Huntingtin aggregates ; Hsc70/Hsp70 ; Syntaxin
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 出版时间：2 March 2007
- 年：2007
- 卷：354
- 期：1
- 页码：39-44
- 全文大小：1062 K
文摘
Huntingtin is a widely expressed 350-kDa cytosolic multidomain of unknown function. Aberrant expansion of the polyglutamine tract located in the N-terminal region of huntingtin results in Huntington’s disease. The presence of insoluble huntingtin inclusions in the brains of patients is one of the hallmarks of Huntington’s disease. Experimentally, both full-length huntingtin and N-terminal fragments of huntingtin with expanded polyglutamine tracts trigger aggregate formation. Here, we report that upon the formation of huntingtin aggregates; endogenous cytosolic huntingtin, Hsc70/Hsp70 (heat shock protein and cognate protein of 70 kDa) and syntaxin 1A become aggregate-centered. This redistribution suggests that these proteins are eventually depleted and become unavailable for normal cellular function. These results indicate that the cellular targeting of several key proteins are altered in the presence of mutant huntingtin and suggest that aggregate depletion of these proteins may underlie, in part, the sequence of disease progression.