Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans.

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.

authors

Satyal SH,Schmidt E,Kitagawa K,Sondheimer N,Lindquist S,Kramer JM,Morimoto RI

doi

10.1073/pnas.100107297

keywords:

subject

Has Abstract

pub_date

2000-05-23 00:00:00

pages

5750-5

issue

11

eissn

0027-8424

issn

1091-6490

pii

100107297

journal_volume

97

pub_type

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