title: [PSI(+) ] prion variant establishment in yeast.
abstract: Differences in the clinical pathology of mammalian prion diseases reflect distinct heritable conformations of aggregated PrP proteins, called prion strains. Here, using the yeast [PSI(+) ] prion, we examine the de novo establishment of prion strains (called variants in yeast). The [PSI(+) ] prion protein, Sup35, is efficiently induced to take on numerous prion variant conformations following transient overexpression of Sup35 in the presence of another prion, e.g. [PIN(+) ]. One hypothesis is that the first [PSI(+) ] prion seed to arise in a cell causes propagation of only that seed's variant, but that different variants could be initiated in different cells. However, we now show that even within a single cell, Sup35 retains the potential to fold into more than one variant type. When individual cells segregating different [PSI(+) ] variants were followed in pedigrees, establishment of a single variant phenotype generally occurred in daughters, granddaughters or great-granddaughters - but in 5% of the pedigrees cells continued to segregate multiple variants indefinitely. The data are consistent with the idea that many newly formed prions go through a maturation phase before they reach a single specific variant conformation. These findings may be relevant to mammalian PrP prion strain establishment and adaptation.
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Sharma
authors.forename: Susan W
authors.initials: SW
authors.lastname: Liebman
mesh_terms: D015870:Gene Expression; D010454:Peptide Termination Factors / Q000737:chemistry / Q000378:metabolism*; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010454:Peptide Termination Factors; D011328:Prions; C080775:SUP45 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins