Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9989595 | Neurobiology of Disease | 2005 | 8 Pages |
Abstract
Accumulation of mutant Huntingtin (Htt), especially the N-terminal-cleaved Htt, participates in the pathophysiology of Huntington's disease (HD). It is difficult to elucidate temporal properties of the translocation of “endogenous” Htt using autopsy HD patient brains. Thus, we examined the cell biology of “endogenous” Htt cleavage and nuclear translocation in cultured lymphoblasts of HD patients and controls. Apoptotic stimulation of lymphoblasts elicits caspase-dependent cleavage and selective nuclear translocation of N-terminal portions of Htt. Discrete clusters of the N-terminal Htt accumulate at unique perinuclear sites prior to nuclear translocation. Our findings suggest that caspase cleavage of Htt is cytoplasmic and precedes sorting to specific perinuclear sites followed by nuclear translocation in HD patient tissue.
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Authors
Akira Sawa, Eiichiro Nagata, Siobhan Sutcliffe, Pratima Dulloor, Matthew B. Cascio, Yuji Ozeki, Sophie Roy, Christopher A. Ross, Solomon H. Snyder,