A non-Q/N-rich prion domain of a foreign prion, [Het-s], can propagate as a prion in yeast.
Prions are self-propagating, infectious aggregates of misfolded proteins. The mammalian prion, PrP(Sc), 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.
Taneja
Vibha
V
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Maddelein
Marie-Lise
ML
Talarek
Nicolas
N
Saupe
Sven J
SJ
Liebman
Susan W
SW
D001216:Asparagine / Q000032:analysis; D003902:Detergents / Q000494:pharmacology; D017353:Gene Deletion; D005973:Glutamine / Q000032:analysis; D006360:Heat-Shock Proteins / Q000378:metabolism; D048468:Podospora / Q000737:chemistry* / Q000187:drug effects; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012521:Sarcosine / Q000031:analogs & derivatives / Q000494:pharmacology
D003902:Detergents; D006360:Heat-Shock Proteins; D011328:Prions; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D005973:Glutamine; C070972:HsP104 protein, S cerevisiae; C025231:sarkosyl; D001216:Asparagine; D012521:Sarcosine