Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2000 May 23;97(11):5750-5.

Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans.

Author information

  • 1Department of Biochemistry, Molecular Biology, and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.

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.

PMID:
10811890
[PubMed - indexed for MEDLINE]
PMCID:
PMC18505
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk