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

[PSI+] is a prion (infectious protein) of Sup35p, a subunit of the Saccharo myces cerevisiae translation termination factor. We isolated a dominant all ele, SSA1-21, of a gene encoding an Hsp70 chaperone that impairs [PSI+] mit otic stability and weakens allosuppression caused by [PSI+]. While [PSI+] s tability 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 partiall y cured of [PSI+] by rapid induction of the heat-shock response but not by growth at 37 degrees. The number of inheritable [PSI+] particles is signifi cantly reduced in SSA1-21 cells. SSA1-21 effects on [PSI+] appear to be ind ependent of Hsp104, another stress-inducible protein chaperone known to be involved in [PSI+] propagation. We propose that cytosolic Hsp70 is importan t for the formation of Sup35p polymers characteristic of [PSI+] from preexi sting material and that Ssa1-21p both lacks and interferes with this activi ty. 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 basa l expression of Hsp104 and SSA1.