Modulation of prion formation, aggregation, and toxicity by the actin cytoskeleton in yeast
Modulation of prion formation, aggregation, and toxicity by the actin cytoskeleton in yeast
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DOI：
10.1128/mcb.26.2.617-629.2006
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发表时间：
2006-01-01
影响因子：
5.3
通讯作者：
Chernoff, YO
中科院分区：
文献类型：
--
作者：
Ganusova, EE;Ozolins, LN;Chernoff, YO
自我延续的蛋白质聚集体在哺乳动物中传播朊病毒疾病，在酵母中传播可遗传的性状。新朊病毒的形成可以通过相应朊病毒形成蛋白或其朊病毒结构域的瞬时过量产生来诱导。在这里，我们证明了酵母朊病毒蛋白Sup 35与肌动蛋白皮质细胞骨架中参与内吞作用的各种蛋白质相互作用。Sup 35衍生的聚集体，在朊病毒诱导的过程中产生的，与内吞/空泡途径的组件。皮质肌动蛋白cytochelleton的突变改变减少聚集过度生产Sup 35和从头朊病毒诱导和增加朊病毒相关的毒性在酵母中。编码肌动蛋白装配蛋白Sla 2的基因的缺失在同时含有Sup 35和Rnq 1蛋白的朊病毒同种型的细胞中是致命的。我们的数据是一致的模型，其中细胞骨架结构，提供了一个支架产生大的聚集体，类似于哺乳动物的侵略。这些聚集体促进朊病毒形成。此外，它似乎肌动蛋白cytochelleton也发挥了一定的作用，在抵消过度生产的潜在聚集蛋白质的毒性。
Self-perpetuating protein aggregates transmit prion diseases in mammals and heritable traits in yeast. De novo prion formation can be induced by transient overproduction of the corresponding prion-forming protein or its prion domain. Here, we demonstrate that the yeast prion protein Sup35 interacts with various proteins of the actin cortical cytoskelleton that are involved in endocytosis. Sup35-derived aggregates, generated in the process of prion induction, are associated with the components of the endocytic/vacuolar pathway. Mutational alterations of the cortical actin cytoskelleton decrease aggregation of overproduced Sup35 and de novo prion induction and increase prion-related toxicity in yeast. Deletion of the gene coding for the actin assembly protein Sla2 is lethal in cells containing the prion isoforms of both Sup35 and Rnq1 proteins simultaneously. Our data are consistent with a model in which cytoskelletal structures,provide a scaffold for generation of large aggregates, resembling mammalian aggresomes. These aggregates promote prion formation. Moreover, it appears that the actin cytoskelleton also plays a certain role in counteracting the toxicity of the overproduced potentially aggregating proteins.