Functionally redundant isoforms of a yeast Hsp70 chaperone subfamily have different anti-prion effects

Why eukaryotes encode multiple Hsp70 isoforms is unclear. Saccharomyces cerevisiae Ssa1p and Ssa2p are constitutive 98% identical Hsp70s. Stress-inducible Ssa3p and Ssa4p are 80% identical to Ssa1/2p. We show Ssa1p-4p have distinct functions affecting [PSI+] and [URE3] prions. When expressed as the only Ssa, Ssa1p antagonized [URE3] and Ssa2p antagonized [PSI+]. Ssa3p and Ssa4p influenced [URE3] and [PSI+] somewhat differently but overall their effects paralleled those of Ssa1p and Ssa2p, respectively. Additionally, Ssa3p suppressed a prion-inhibitory effect of elevated temperature. Our previously described Ssa1-21p mutant weakens [PSI+] in SSA1-21 SSA2 cells and abolishes it in SSA1-21 ssa2 cells. To test if the same mutation affected other prions or altered Ssa2p similarly, we compared effects of a constructed Ssa2-21p mutant and Ssa1-21p on both prions. Surprisingly, [URE3] was unaffected in SSA1-21 SSA2 cells and could propagate in SSA1-21 ssa2 cells. Ssa2-21p impaired [URE3] considerably and weakened [PSI+] strongly but in a manner distinct from Ssa1-21p, highlighting functional differences between these nearly identical Hsp70s. Our data uncover exquisite functional differences among isoforms of a highly homologous cytosolic Hsp70 subfamily and point to a possibility that variations in Hsp70 function that might improve fitness under optimal conditions are also important during stress.

Key Words: chaperone, hsp70, prion, yeast

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