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Updated: May 18, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
[PSI(+) ] prion variant establishment in yeast
1Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
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.
Insights
Yeast prions, or variants, can develop multiple conformations within a single cell. Some cells indefinitely maintain diverse prion variants, suggesting a maturation phase before a single conformation is established.
Area of Science:
- Biochemistry
- Molecular Biology
- Yeast Genetics
Background:
- Mammalian prion diseases exhibit distinct clinical pathologies due to heritable conformations of aggregated PrP proteins, known as prion strains.
- The yeast [PSI(+) ] prion, mediated by the Sup35 protein, serves as a model for studying prion strain establishment.
- Transient overexpression of Sup35, particularly in the presence of the [PIN(+) ] prion, can induce diverse prion variant conformations.
Purpose of the Study:
- To investigate the de novo establishment of prion strains, termed variants, in the yeast model system.
- To determine if a single cell can harbor and propagate multiple prion variants simultaneously.
- To explore the potential maturation process of newly formed prions before they stabilize into a specific variant conformation.
Main Methods:
- Utilizing the yeast [PSI(+) ] prion model with Sup35 protein overexpression.
- Employing the [PIN(+) ] prion to facilitate the induction of new [PSI(+) ] variants.
- Tracking the segregation of prion variants within cell pedigrees over multiple generations.
Main Results:
- Transient overexpression of Sup35 can induce multiple prion variants within a single yeast cell.
- While most cells stabilize to a single variant phenotype, approximately 5% of pedigrees indefinitely segregated multiple [PSI(+) ] variants.
- This suggests that newly formed prions may undergo a maturation phase, allowing for the coexistence and potential diversification of variants.
Conclusions:
- The yeast prion system demonstrates that multiple prion variants can arise and coexist within a single cell.
- The findings support a model where newly formed prions mature over time, potentially explaining the establishment and adaptation of prion strains.
- These insights into yeast prion variant dynamics may offer relevant perspectives on the mechanisms underlying mammalian PrP prion strain establishment and adaptation.
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