Abstract:
:Expansion of polyglutamine repeats in several unrelated proteins causes neurodegenerative diseases with distinct but related pathologies. To provide a model system for investigating common pathogenic features, we have examined the behavior of polyglutamine expansions expressed in Caenorhabditis elegans. The expression of polyglutamine repeats as green fluorescent protein (GFP)-fusion proteins in body wall muscle cells causes discrete cytoplasmic aggregates that appear early in embryogenesis and correlates with a delay in larval to adult development. The heat shock response is activated idiosyncratically in individual cells in a polyglutamine length-dependent fashion. The toxic effect of polyglutamine expression and the formation of aggregates can be reversed by coexpression of the yeast chaperone Hsp104. The altered homeostasis associated with polyglutamine aggregates causes both the sequestration of an otherwise soluble protein with shorter arrays of glutamine repeats and the relocalization of a nuclear glutamine-rich protein. These observations of induced aggregation and relocalization have implications for disorders involving protein aggregation.
journal_name
Proc Natl Acad Sci U S Aauthors
Satyal SH,Schmidt E,Kitagawa K,Sondheimer N,Lindquist S,Kramer JM,Morimoto RIdoi
10.1073/pnas.100107297keywords:
subject
Has Abstractpub_date
2000-05-23 00:00:00pages
5750-5issue
11eissn
0027-8424issn
1091-6490pii
100107297journal_volume
97pub_type
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