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A size threshold limits prion transmission and establishes phenotypic diversity.

ABSTRACT: According to the prion hypothesis, atypical phenotypes arise when a prion protein adopts an alternative conformation and persist when that form assembles into self-replicating aggregates. Amyloid formation in vitro provides a model for this protein-misfolding pathway, but the mechanism by which this process interacts with the cellular environment to produce transmissible phenotypes is poorly understood. Using the yeast prion Sup35/[PSI(+)], we found that protein conformation determined the size distribution of aggregates through its interactions with a molecular chaperone. Shifts in this range created variations in aggregate abundance among cells because of a size threshold for transmission, and this heterogeneity, along with aggregate growth and fragmentation, induced age-dependent fluctuations in phenotype. Thus, prion conformations may specify phenotypes as population averages in a dynamic system.

SUBMITTER: Derdowski A

PROVIDER: S-EPMC3003433 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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A size threshold limits prion transmission and establishes phenotypic diversity.

Derdowski Aaron A Sindi Suzanne S SS Klaips Courtney L CL DiSalvo Susanne S Serio Tricia R TR

Science (New York, N.Y.) 20101001 6004

According to the prion hypothesis, atypical phenotypes arise when a prion protein adopts an alternative conformation and persist when that form assembles into self-replicating aggregates. Amyloid formation in vitro provides a model for this protein-misfolding pathway, but the mechanism by which this process interacts with the cellular environment to produce transmissible phenotypes is poorly understood. Using the yeast prion Sup35/[PSI(+)], we found that protein conformation determined the size ...[more]

PMID: 21030659

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