Document Detail

Localization of HET-S to the cell periphery, not to [Het-s] aggregates, is associated with [Het-s]-HET-S toxicity.
MedLine Citation:
PMID:  22037764     Owner:  NLM     Status:  MEDLINE    
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-/nonself-discrimination process. Here, using the prion form of a fragment of HET-s ([PrD(157)(+)]), we show that [Het-s]-HET-S toxicity can be faithfully recapitulated in yeast. Overexpression of Hsp40 chaperone, Sis1, rescues this toxicity by curing cells of [PrD(157)(+)]. We find no evidence for toxic [PrD(157)(+)] conformers in the presence of HET-S. Instead, [PrD(157)(+)] appears to seed HET-S to accumulate at the cell periphery and to form aggregates distinct from visible [PrD(157)(+)] aggregates. Furthermore, HET-S mutants that cause HET-S to be sequestered into [PrD(157)(+)] 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 relocalization, rather than the formation of mixed HET-s/HET-S aggregates, is associated with toxicity.
Vidhu Mathur; Carolin Seuring; Roland Riek; Sven J Saupe; Susan W Liebman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-10-28
Journal Detail:
Title:  Molecular and cellular biology     Volume:  32     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-14     Completed Date:  2012-02-13     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  139-53     Citation Subset:  IM    
Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
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MeSH Terms
Amyloid / analysis,  genetics,  metabolism*
Fungal Proteins / analysis*,  genetics,  metabolism*
Gene Expression
HSP40 Heat-Shock Proteins / genetics
Podospora / cytology*,  genetics,  metabolism
Prions / analysis,  genetics,  metabolism*
Protein Multimerization
Protein Structure, Tertiary
Grant Support
Reg. No./Substance:
0/Amyloid; 0/Fungal Proteins; 0/HSP40 Heat-Shock Proteins; 0/Prions

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