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Localization of HET-S to the cell periphery, and not to [Het-s] aggregates, is associated with [Het-s]-HET-S toxicity

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Title: Localization of HET-S to the cell periphery, and not to [Het-s] aggregates, is associated with [Het-s]-HET-S toxicity
Alternative Title: [Het-s]/HET-S toxicity
Author(s): Mathur, V.; Seuring, C.; Riek, R.; Saupe, S. J.; Liebman, S. W.
Abstract: Prion diseases are associated with accumulation of the amyloid form of the prion protein, but the mechanisms of toxicity are unknown. Amyloid toxicity is also associated with fungal prions. In Podospora anserina, the simultaneous presence of [Het-s] prion and its allelic protein HET-S causes cell death in a self/non-self discrimination process. Here, using the prion form of a fragment of HET-s ([PrD157 +]), we show that [Hets]/ HET-S toxicity can be faithfully recapitulated in yeast. Overexpression of Hsp40 chaperone, Sis1, rescues this toxicity by curing cells of [PrD157 +]. We find no evidence for toxic [PrD157 +] conformers in the presence of HET-S. Instead, [PrD157 +] appears to seed HET-S to accumulate at the cell periphery and to form aggregates distinct from visible [PrD157 +] aggregates. Furthermore, HET-S mutants that cause HET-S to be sequestered into [PrD157 +] prion aggregates are not toxic. The localization of HET-S at the cell periphery and its association with cell death was also observed in the native host Podospora anserina. Thus, upon interaction with [Het-s], HET-S localizes to the cell periphery and this re-localization, rather than the formation of mixed HET-s/HET-S aggregates, is associated with toxicity.
Issue Date: 2012-01
Publisher: American Society for Microbiology
Citation Info: Mathur, V., Seuring, C., Riek, R., Saupe, S. J., & Liebman, S. W. 2012. Localization of HET-S to the Cell Periphery, Not to [Het-s] Aggregates, Is Associated with [Het-s]-HET-S Toxicity. Molecular and Cellular Biology, 32(1): 139-153. DOI: 10.1128/MCB.06125-11
Type: Article
Description: Post print version of article may differ from published version. The definitive version is available through American Society for Microbiology at DOI: 10.1128/MCB.06125-11
ISSN: 0270-7306
Date Available in INDIGO: 2012-03-06

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