A role for cytosolic Hsp70 in yeast [PSI+] prion propagation and [PSI+] as a cellular stress

Abstract

[PSI+] is a prion (infectious protein) of Sup35p, a subunit of the Saccharomyces cerevisiae translation termination factor. We isolated a dominant allele, SSA1-21, of a gene encoding an Hsp70 chaperone that impairs [PSI+] mitotic stability, and weakens allosuppression caused by [PSI+]. While [PSI+] stability is normal in strains lacking SSA1, SSA2, or both, SSA1-21 strains with a deletion of SSA2 cannot propagate [PSI+]. SSA1-21 [PSI+] strains are hypersensitive to curing of [PSI+] by guanidine-hydrochloride and partially cured of [PSI+] by rapid induction of the heat-shock response but not by growth at 37°. The number of inheritable [PSI+] particles is significantly reduced in SSA1-21 cells. SSA1-21 effects on [PSI+] appear to be independent of Hsp104, another stress-inducible protein chaperone known to be involved in [PSI+] propagation. We propose that cytosolic Hsp70 is important for the formation of Sup35p polymers characteristic of [PSI+] from preexisting material and that Ssa1-21p both lacks and interferes with this activity. We further demonstrate that the negative effect of heat stress on [PSI+] phenotype directly correlates with solubility of Sup35p and find that in wild-type strains the presence of [PSI+] causes a stress that elevates basal expression of Hsp104 and SSA1.