Extracellular Vesicles-Encapsulated Yeast Prions and What They Can Tell Us about the Physical Nature of Propagons.

Extracellular Vesicles-Encapsulated Yeast Prions and What They Can Tell Us about the Physical Nature of Propagons.
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DOI:
10.3390/ijms22010090
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发表时间:
2020-12-23
影响因子:
5.6
通讯作者:
Kabani M
Kabani M
中科院分区:
生物学2区
文献类型:
--
作者:
Kabani M

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酿酒酵母(Saccharomyces cerevisiae)具有一系列基于蛋白质的遗传性状,其中大部分是由结构和功能多样的细胞质蛋白转化为朊病毒形式引起的。其中,[PSI+]、[URE 3]和[PIN+]是文献记载最多的朊病毒,分别由Sup 35 p、Ure 2 p和Rnq 1 p组装成不溶性纤维状组装体而产生。酵母朊病毒通过分子伴侣介导的这些聚集体的片段化来繁殖,这产生小的自模板种子或繁殖体。繁殖体的确切分子性质以及它们如何忠实地从母体细胞传递到子细胞,尽管空间蛋白质质量控制尚未完全了解。在[PSI+]细胞中,Sup 35 p在半变性条件下形成可在琼脂糖凝胶上检测到的耐洗涤剂组装体,并且当蛋白质与绿色荧光蛋白(GFP)融合时形成胞质荧光斑点;然而,[PSI+]的这些宏观表现与通过蛋白质感染测定法在生长期间测量的感染性不完全相关。我们还发现,大量的感染性Sup 35 p颗粒通过细胞外(EV)和周质(PV)囊泡在生长阶段和葡萄糖依赖性的方式输出。在本综述中,我将讨论如何这些囊泡可能是一个来源的实际繁殖和一个合适的车辆,他们的传输到芽。
The yeast Saccharomyces cerevisiae hosts an ensemble of protein-based heritable traits, most of which result from the conversion of structurally and functionally diverse cytoplasmic proteins into prion forms. Among these, [PSI+], [URE3] and [PIN+] are the most well-documented prions and arise from the assembly of Sup35p, Ure2p and Rnq1p, respectively, into insoluble fibrillar assemblies. Yeast prions propagate by molecular chaperone-mediated fragmentation of these aggregates, which generates small self-templating seeds, or propagons. The exact molecular nature of propagons and how they are faithfully transmitted from mother to daughter cells despite spatial protein quality control are not fully understood. In [PSI+] cells, Sup35p forms detergent-resistant assemblies detectable on agarose gels under semi-denaturant conditions and cytosolic fluorescent puncta when the protein is fused to green fluorescent protein (GFP); yet, these macroscopic manifestations of [PSI+] do not fully correlate with the infectivity measured during growth by the mean of protein infection assays. We also discovered that significant amounts of infectious Sup35p particles are exported via extracellular (EV) and periplasmic (PV) vesicles in a growth phase and glucose-dependent manner. In the present review, I discuss how these vesicles may be a source of actual propagons and a suitable vehicle for their transmission to the bud.
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