Environmental Regulation of Prions in Yeast 英文参考文献.docVIP

Pearls EnvironmentalRegulationofPrionsinYeast LimingLi*,AnthonyS.Kowal DepartmentofMolecularPharmacologyandBiologicalChemistry,TheFeinbergSchoolofMedicine,NorthwesternUniversity,Chicago,Illinois,UnitedStatesofAmerica TheYeastPrionConcept nonprion recipient haploid progeny without exchange of genetic information.This‘‘gold-standard’’assayhasbeenusedtoconfirm if a phenotypic trait is cytoplamically inherited; all known yeast prionsarecytoducibleduetotheirprotein-basedinfectivity.Prion infectivity can also be demonstrated by transformation of prion fibrils (Figure 1C). Incubating na?¨ve [prion2] cells with amyloid fibrilsassembledinvitrofromrecombinantprionproteinscanresult indenovoformationofstable,transmissibleprionsintherecipient. The first successful studies to demonstrate fibril-based transfor- Thetermprion,proteinaceusinfectiousparticle,wasfirstused to describe the causative agent of a group of mammalian neurodegenerative diseases known as transmissible spongiform encephalopathies(TSEs)[1].Themammalianprionprotein(PrP) can exist in either a normal cellular conformation, PrPC, or in multiple misfolded pathogenic conformations, collectively called PrPSc. PrPSc is considered infectious because it can recruit and convert its normal isomer PrPC to its pathogenic conformation. + mation were conducted using the well-studied prion [PSI ], a This ‘‘protein-only’’ concept of infectivity has gained general acceptanceandhasbeenextendedtoexplainsomeunusualnon- Mendelian genetic elements in the budding yeast Saccharomyces cerevisiae. In yeast, these factorsare transmitted from mother to daughtercellasparticularself-propagatingproteinconformations, andarethusreferredtoasyeastprions[2]. YeastprionssharemanyfeatureswithPrPSc:botharecapable of perpetuating particular conformational changes, forming amyloid fibrils (ordered protein aggregates with cross-b sheet translation termination modifier [5,6]. This method of transfor- mation provides simple, direct confirmation that t