title: An insight into the complex prion-prion interaction network in the budding yeast Saccharomyces cerevisiae.
abstract: The budding yeast Saccharomyces cerevisiae is a valuable model system for studying prion-prion interactions as it contains multiple prion proteins. A recent study from our laboratory showed that the existence of Swi1 prion ([SWI(+)]) and overproduction of Swi1 can have strong impacts on the formation of 2 other extensively studied yeast prions, [PSI(+)] and [PIN(+)] ([RNQ(+)]) (Genetics, Vol. 197, 685-700). We showed that a single yeast cell is capable of harboring at least 3 heterologous prion elements and these prions can influence each other's appearance positively and/or negatively. We also showed that during the de novo [PSI(+)] formation process upon Sup35 overproduction, the aggregation patterns of a preexisting inducer ([RNQ(+)] or [SWI(+)]) can undergo significant remodeling from stably transmitted dot-shaped aggregates to aggregates that co-localize with the newly formed Sup35 aggregates that are ring/ribbon/rod- shaped. Such co-localization disappears once the newly formed [PSI(+)] prion stabilizes. Our finding provides strong evidence supporting the "cross-seeding" model for prion-prion interactions and confirms earlier reports that the interactions among different prions and their prion proteins mostly occur at the initiation stages of prionogenesis. Our results also highlight a complex prion interaction network in yeast. We believe that elucidating the mechanism underlying the yeast prion-prion interaction network will not only provide insight into the process of prion de novo generation and propagation in yeast but also shed light on the mechanisms that govern protein misfolding, aggregation, and amyloidogenesis in higher eukaryotes.
authors.affiliation: a Department of Biochemistry and Molecular Genetics , the Feinberg School of Medicine ; Northwestern University ; Chicago , IL USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Du
authors.forename: Stephanie
authors.initials: S
authors.lastname: Valtierra
authors.forename: Liming
authors.initials: L
authors.lastname: Li
mesh_terms: D000682:Amyloid / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008954:Models, Biological; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding; D017510:Protein Folding; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*
chemical_list: D000682:Amyloid; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins
keywords: Saccharomyces cerevisiae; [PIN+]; [PSI+]; [SWI+]; amyloid; prion; prion interactions; protein aggregation; yeast