title: Function of SSA subfamily of Hsp70 within and across species varies widely in complementing Saccharomyces cerevisiae cell growth and prion propagation.
abstract: BACKGROUND
  The cytosol of most eukaryotic cells contains multiple highly conserved Hsp70 orthologs that differ mainly by their spatio-temporal expression patterns. Hsp70s play essential roles in protein folding, transport or degradation, and are major players of cellular quality control processes. However, while several reports suggest that specialized functions of Hsp70 orthologs were selected through evolution, few studies addressed systematically this issue.
  
  
  RESULTS
  We compared the ability of Ssa1p-Ssa4p from Saccharomyces cerevisiae and Ssa5p-Ssa8p from the evolutionary distant yeast Yarrowia lipolytica to perform Hsp70-dependent tasks when expressed as the sole Hsp70 for S. cerevisiae in vivo. We show that Hsp70 isoforms (i) supported yeast viability yet with markedly different growth rates, (ii) influenced the propagation and stability of the [PSI(+)] and [URE3] prions, but iii) did not significantly affect the proteasomal degradation rate of CFTR. Additionally, we show that individual Hsp70 orthologs did not induce the formation of different prion strains, but rather influenced the aggregation properties of Sup35 in vivo. Finally, we show that [URE3] curing by the overexpression of Ydj1p is Hsp70-isoform dependent.
  
  
  CONCLUSIONS
  Despite very high homology and overlapping functions, the different Hsp70 orthologs have evolved to possess distinct activities that are required to cope with different types of substrates or stress situations. Yeast prions provide a very sensitive model to uncover this functional specialization and to explore the intricate network of chaperone/co-chaperone/substrates interactions.
authors.affiliation: Laboratory of Biochemistry and Genetics, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.forename: Céline N
authors.initials: CN
authors.lastname: Martineau
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Le Dall
authors.forename: Michael
authors.initials: M
authors.lastname: Reidy
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Masison
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kabani
mesh_terms: D001704:Biopolymers; D002455:Cell Division; D005656:Fungal Proteins / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D008856:Microscopy, Fluorescence; D011328:Prions; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology*; D013045:Species Specificity; D025062:Yarrowia / Q000502:physiology*
chemical_list: D001704:Biopolymers; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D011328:Prions
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