Du Zhiqiang, Valtierra Stephanie, Li Liming
a Department of Biochemistry and Molecular Genetics , the Feinberg School of Medicine ; Northwestern University ; Chicago , IL USA.
Prion. 2014;8(6):387-92. doi: 10.4161/19336896.2014.992274.
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.
出芽酵母酿酒酵母是研究朊病毒 - 朊病毒相互作用的重要模型系统，因为它含有多种朊病毒蛋白。我们实验室最近的一项研究表明，Swi1朊病毒（[SWI(+)]）的存在以及Swi1的过量表达会对另外两种经过广泛研究的酵母朊病毒[PSI(+)]和[PIN(+)]（[RNQ(+)]）的形成产生强烈影响（《遗传学》，第197卷，685 - 700页）。我们发现单个酵母细胞能够容纳至少3种异源朊病毒元件，并且这些朊病毒可以相互正向和/或负向影响彼此的出现。我们还表明，在Sup35过量表达导致从头形成[PSI(+)]的过程中，预先存在的诱导物（[RNQ(+)]或[SWI(+)]）的聚集模式会发生显著重塑，从稳定传播的点状聚集体转变为与新形成的呈环/带/棒状的Sup35聚集体共定位的聚集体。一旦新形成的[PSI(+)]朊病毒稳定下来，这种共定位就会消失。我们的发现为朊病毒 - 朊病毒相互作用的“交叉播种”模型提供了有力证据，并证实了早期的报道，即不同朊病毒及其朊病毒蛋白之间的相互作用大多发生在朊病毒形成的起始阶段。我们的结果还突出了酵母中复杂的朊病毒相互作用网络。我们相信，阐明酵母朊病毒 - 朊病毒相互作用网络的潜在机制不仅将为酵母中朊病毒的从头产生和传播过程提供见解，还将揭示高等真核生物中控制蛋白质错误折叠、聚集和淀粉样蛋白形成的机制。
