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Updated: Jun 7, 2026
08:12
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
A size threshold limits prion transmission and establishes phenotypic diversity
Aaron Derdowski1, Suzanne S Sindi, Courtney L Klaips
1Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 185 Meeting Street, Post Office Box G-L2, Providence, RI 02912, USA.
Science (New York, N.Y.)
|October 30, 2010
Summary
Prion protein conformations influence aggregate size, affecting transmission and causing age-dependent phenotype variations. This suggests prion conformations specify phenotypes as dynamic population averages.
Area of Science:
- Biochemistry
- Molecular Biology
- Yeast Genetics
Background:
- The prion hypothesis posits that altered protein conformations lead to self-replicating aggregates, causing atypical phenotypes.
- Understanding how these protein misfolding pathways interact with cellular environments to produce transmissible phenotypes remains a challenge.
Purpose of the Study:
- To investigate the relationship between prion protein conformation, aggregate characteristics, and phenotype variability in a cellular context.
- To elucidate the mechanisms underlying prion-mediated phenotypic inheritance and fluctuation.
Main Methods:
- Utilized the yeast prion model system (Sup35/[PSI(+)]) to study prion protein aggregation.
- Analyzed the impact of protein conformation on aggregate size distribution through interactions with molecular chaperones.
- Investigated the role of aggregate abundance, transmission thresholds, growth, and fragmentation in phenotypic variation.
Main Results:
- Protein conformation was found to dictate the size distribution of prion aggregates via chaperone interactions.
- Variations in aggregate size led to differential aggregate abundance among cells due to a transmission size threshold.
- Aggregate dynamics (growth, fragmentation) and cell-to-cell heterogeneity resulted in age-dependent phenotype fluctuations.
Conclusions:
- Prion protein conformations can determine phenotypes by influencing aggregate dynamics and cellular heterogeneity.
- Phenotypic outcomes in prion systems may be best understood as population averages within a dynamic, stochastic environment.
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