De novo [PSI +] prion formation involves multiple pathways to form infectious oligomers.
De novo [PSI +] prion formation involves multiple pathways to form infectious oligomers.
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[PSI]朊病毒从头形成涉及形成感染性寡聚体的多种途径。
DOI：
10.1038/s41598-017-00135-6
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发表时间：
2017
影响因子：
4.6
通讯作者：
Manogaran,AnitaL
中科院分区：
文献类型：
--
作者：
Sharma,Jaya;Wisniewski,BrettT;Paulson,Emily;Obaoye,JoannaO;Merrill,StephenJ;Manogaran,AnitaL
朊病毒和其他神经退行性疾病与称为淀粉样蛋白的错误折叠蛋白质组装有关。研究已经开始揭示淀粉样蛋白传播的共同机制，但淀粉样蛋白如何在体内形成仍不清楚。在这里，我们利用酵母朊病毒[PSI+]来揭示体内淀粉样蛋白形成的早期步骤。[PSI+]是Sup 35蛋白的朊病毒形式。虽然[PSI+]的形成是相当罕见的，朊病毒可以大大诱导过表达的朊病毒结构域的Sup 35蛋白。当朊病毒结构域与GFP融合时，[PSI+]的这种新诱导显示荧光胞质环的出现。我们目前的工作表明，新归纳比以前认为的更复杂。使用4D活细胞成像，我们观察到荧光结构是通过四种不同的途径形成的，以产生[PSI+]细胞。新生诱导培养物的生化分析表明，新形成的SDS抗性寡聚体的大小随时间而变化，由新生诱导培养物制备的裂解物能够将[psi-]细胞转化为[PSI+]细胞。总之，我们的研究结果表明，新形成的朊病毒寡聚体是传染性的。
Prion and other neurodegenerative diseases are associated with misfolded protein assemblies called amyloid. Research has begun to uncover common mechanisms underlying transmission of amyloids, yet how amyloids forminvivois still unclear. Here, we take advantage of the yeast prion, [PSI+],to uncover the early steps of amyloid formationin vivo.[PSI+] is the prion form of the Sup35 protein. While [PSI+] formation is quite rare, the prion can be greatly induced by overexpression of the prion domain of the Sup35 protein. Thisde novoinduction of [PSI+] shows the appearance of fluorescent cytoplasmic rings when the prion domain is fused with GFP. Our current work shows thatde novoinduction is more complex than previously thought. Using 4D live cell imaging, we observed that fluorescent structures are formed by four different pathways to yield [PSI+] cells. Biochemical analysis ofde novoinduced cultures indicates that newly formed SDS resistant oligomers change in size over time and lysates made fromde novoinduced cultures are able to convert [psi−] cells to [PSI+] cells. Taken together, our findings suggest that newly formed prion oligomers are infectious.