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© The Rockefeller University Press, 0021-9525/2002/6/905-b $5.00
The Journal of Cell Biology, Volume 157, Number 6, June 10, 2002 905-b-905

A Prion in yeast Huntington's disease

Huntingtin-like proteins make yeast sick (bottom).

Meriin et al., reporting on page 997, have developed the first yeast model for studying Huntington's disease. Yeast cannot undergo neurodegeneration, of course, but the simplicity and genetic manipulability of the system are already providing important mechanistic insights. The authors report that aggregation of a polypeptide with an expanded polyglutamine domain, mediated by a prion-like protein, is responsible for cell death in their system, suggesting revisions to earlier models of neurodegeneration.

In Huntington's disease, expansion of the huntingtin polyglutamine domain leads to protein aggregation in inclusion bodies and neuronal cell death. In some systems, however, long polyglutamine peptides are toxic without aggregating, suggesting that aggregation of mutant huntingtin might not determine toxicity. Meriin and colleagues found, however, that aggregation of long polyglutamine peptides in yeast correlated with toxicity. Mutations in certain chaperone genes, or curing the cells of the prion form of the Rnq1 protein, suppressed both aggregation and toxicity.

The results directly link polyglutamine peptide aggregation with cell death, and demonstrate that prion proteins are required for this process, at least in yeast. The evolutionary conservation of these mechanisms suggests that prion-like proteins might also be involved in mammalian polyglutamine expansion diseases.

Alan W. Dove

alanwdove{at}earthlink.net

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Huntingtin toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1

Anatoli B. Meriin, Xiaoqian Zhang, Xiangwei He, Gary P. Newnam, Yury O. Chernoff, and Michael Y. Sherman
J. Cell Biol. 2002 157: 997-1004. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 295K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?