Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans

Sanjeev H. Satyal, Enrico Schmidt, Kazunori Kitagawa, Neal Sondheimer, Susan Lindquist, James M. Kramer, Richard I. Morimoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

315 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5750-5755
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number11
DOIs
StatePublished - May 23 2000

ASJC Scopus subject areas

  • General

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