NR AXEZ
AU Taneja,V.; Maddelein,M.L.; Talarek,N.; Saupe,S.J.; Liebman,S.W.
TI A non-Q/N-rich prion domain of a foreign prion, [Het-s], can propagate as a prion in yeast
QU Molecular Cell 2007 Jul 6; 27(1): 67-77
PT journal article; research support, n.i.h., extramural; research support, non-u.s. gov't
AB Prions are self-propagating, infectious aggregates of misfolded proteins. The mammalian prion, PrPsc, causes fatal neurodegenerative disorders. Fungi also have prions. While yeast prions depend upon glutamine/asparagine (Q/N)-rich regions, the Podospora anserina HET-s and PrP prion proteins lack such sequences. Nonetheless, we show that the HET-s prion domain fused to GFP propagates as a prion in yeast. Analogously to native yeast prions, transient overexpression of the HET-s fusion induces ring-like aggregates that propagate in daughter cells as cytoplasmically inherited, detergent-resistant dot aggregates. Efficient dot propagation, but not ring formation, is dependent upon the Hsp104 chaperone. The yeast prion [PIN(+)] enhances HET-s ring formation, suggesting that prions with and without Q/N-rich regions interact. Finally, HET-s aggregates propagated in yeast are infectious when introduced into Podospora. Taken together, these results demonstrate prion propagation in a truly foreign host. Since yeast can host non-Q/N-rich prions, such native yeast prions may exist.
MH Asparagine/analysis; Detergents/pharmacology; Gene Deletion; Glutamine/analysis; Heat-Shock Proteins/metabolism; Podospora/*chemistry/drug effects; Prions/*chemistry/*metabolism; Protein Structure, Quaternary; Protein Structure, Tertiary; Recombinant Fusion Proteins/metabolism; Saccharomyces cerevisiae/cytology/drug effects/*metabolism; Saccharomyces cerevisiae Proteins/metabolism; Sarcosine/analogs & derivatives/pharmacology
AD Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
SP englisch
PO USA