HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 52, 37694-37701, December 28, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/52/37694    most recent M705211200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Li, L.-B. Articles by Bonini, N. M. Search for Related Content PubMed PubMed Citation Articles by Li, L.-B. Articles by Bonini, N. M. Social Bookmarking                      What's this?

Suppression of Polyglutamine Toxicity by the Yeast Sup35 Prion Domain in Drosophila^*

Ling-Bo Li¹, Kexiang Xu, and Nancy M. Bonini, Investigator of the Howard Hughes Medical Institute²

From the Department of Biology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018

The propensity of proteins to form β-sheet-rich amyloid fibrils is related to a variety of biological phenomena, including a number of human neurodegenerative diseases and prions. A subset of amyloidogenic proteins forms amyloid fibrils through glutamine/asparagine (Q/N)-rich domains, such as pathogenic polyglutamine (poly(Q)) proteins involved in neurodegenerative disease, as well as yeast prions. In the former, the propensity of an expanded poly(Q) tract to abnormally fold confers toxicity on the respective protein, leading to neuronal dysfunction. In the latter, Q/N-rich prion domains mediate protein aggregation important for epigenetic regulation. Here, we investigated the relationship between the pathogenic ataxin-3 protein of the human disease spinocerebellar ataxia type 3 (SCA3) and the yeast prion Sup35, using Drosophila as a model system. We found that the capacity of the Sup35 prion domain to mediate protein aggregation is conserved in Drosophila. Although select yeast prions enhance poly(Q) toxicity in yeast, the Sup35N prion domain suppressed poly(Q) toxicity in the fly. Suppression required the oligopeptide repeat of the Sup35N prion domain, which is critical for prion properties in yeast. These results suggest a trans effect of prion domains on pathogenic poly(Q) disease proteins in a multicellular environment and raise the possibility that Drosophila may allow studies of prion mechanisms.

Received for publication, June 25, 2007 , and in revised form, October 1, 2007.

^* This work was supported by the NINDS, National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Present address: Dept. of Biochemistry, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112

² To whom correspondence should be addressed: Dept. of Biology, 306 Leidy Laboratory, Howard Hughes Medical Institute, University of Pennsylvania, 415 S. University Ave., Philadelphia, PA 19104-6018. Tel.: 215-573-9267; Fax: 215-573-5754; E-mail: nbonini{at}sas.upenn.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?