Ssa1 overexpression and [PIN(+)] variants cure [PSI(+)] by dilution of aggregates.
Several cellular chaperones have been shown to affect the propagation of the yeast prions [PSI(+)], [PIN(+)] and [URE3]. Ssa1 and Ssa2 are Hsp70 family chaperones that generally cause pro-[PSI(+)] effects, since dominant-negative mutants of Ssa1 or Ssa2 cure [PSI(+)], and overexpression of Ssa1 enhances de novo [PSI(+)] appearance and prevents curing by excess Hsp104. In contrast, Ssa1 was shown to have anti-[URE3] effects, since overexpression of Ssa1 cures [URE3]. Here we show that excess Ssa1 or Ssa2 can also cure [PSI(+)]. This curing is enhanced in the presence of [PIN(+)]. During curing, Sup35-GFP fluorescent aggregates get bigger and fewer in number, which leads to their being diluted out during cell division, a phenotype that was also observed during the curing of [PSI(+)] by certain variants of [PIN(+)]. The sizes of the detergent-resistant [PSI(+)] prion oligomers increase during [PSI(+)] curing by excess Ssa1. Excess Ssa1 likewise leads to an increase in oligomer sizes of low, medium and very high [PIN(+)] variants. While these phenotypes are also caused by inhibition of Hsp104 or Sis1, the overexpression of Ssa1 did not cause any change in Hsp104 or Sis1 levels.
Mathur
Vidhu
V
Department of Biological Sciences, University of Illinois at Chicago, 60607, USA.
Hong
Joo Y
JY
Liebman
Susan W
SW
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D018628:Gene Dosage; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D010454:Peptide Termination Factors; D011328:Prions / Q000037:antagonists & inhibitors*; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D010454:Peptide Termination Factors; D011328:Prions; C542288:SSA2 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae