Document Type

Article

Language

eng

Format of Original

13 p.

Publication Date

5-2011

Publisher

Public Library of Science (PLoS)

Source Publication

PLoS Genetics

Source ISSN

1553-7404

Original Item ID

DOI: 10.1371/journal.pgen.1001386

Abstract

Prions are self-perpetuating aggregated proteins that are not limited to mammalian systems but also exist in lower eukaryotes including yeast. While much work has focused around chaperones involved in prion maintenance, including Hsp104, little is known about factors involved in the appearance of prions. De novo appearance of the [PSI+] prion, which is the aggregated form of the Sup35 protein, is dramatically enhanced by transient overexpression of SUP35 in the presence of the prion form of the Rnq1 protein, [PIN+]. When fused to GFP and overexpressed in [ps2] [PIN+] cells, Sup35 forms fluorescent rings, and cells with these rings bud off [PSI+] daughters. We investigated the effects of over 400 gene deletions on this de novo induction of [PSI+]. Two classes of gene deletions were identified. Class I deletions (bug1D, bem1D, arf1D, and hog1D) reduced the efficiency of [PSI+] induction, but formed rings normally. Class II deletions (las17D, vps5D, and sac6D) inhibited both [PSI+] induction and ring formation. Furthermore, class II deletions reduced, while class I deletions enhanced, toxicity associated with the expanded glutamine repeats of the huntingtin protein exon 1 that causes Huntington’s disease. This suggests that prion formation and polyglutamine aggregation involve a multi-phase process that can be inhibited at different steps.

Comments

Published version. PLoS Genetics, 7(5): e1001386 (May 2011): DOI.© 2011 Manogaran et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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