Facilitated aggregation of FG nucleoporins under molecular crowding conditions
Facilitated aggregation of FG nucleoporins under molecular crowding conditions
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DOI：
10.1038/embor.2012.204
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发表时间：
2013-02-01
期刊：
影响因子：
7.7
通讯作者：
Lemke, Edward A.
中科院分区：
文献类型：
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作者：
Milles, Sigrid;Khanh Huy Bui;Lemke, Edward A.
核内无序和富含苯丙氨酸-甘氨酸的核孔蛋白（FG Nups）在NPC内形成了一个拥挤的和选择性的转运通道，只能在核转运受体（NTR）的帮助下转运。体外研究表明，FG Nups可以组装成两种不同的外观，淀粉样蛋白和水凝胶。这些现象是否以及如何联系在一起，以及它们是否具有生理作用，仍然不清楚。使用各种高分辨率荧光和电子显微镜（EM）工具，我们揭示了模拟NPC环境的拥挤条件可以加速酵母和人FG Nups的聚集和淀粉样蛋白形成速度。聚集可以被NTR抑制，这为细胞如何控制FG Nups的淀粉样蛋白形成提供了理论基础。EM的高超空间分辨能力还揭示了水凝胶是缠绕的淀粉样纤维，这些发现对现有的运输模型和NPC组装有影响。
Intrinsically disordered and phenylalanine-glycine-rich nucleoporins (FG Nups) form a crowded and selective transport conduit inside the NPC that can only be transited with the help of nuclear transport receptors (NTRs). It has been shown in vitro that FG Nups can assemble into two distinct appearances, amyloids and hydrogels. If and how these phenomena are linked and if they have a physiological role still remains unclear. Using a variety of high-resolution fluorescence and electron microscopic (EM) tools, we reveal that crowding conditions mimicking the NPC environment can accelerate the aggregation and amyloid formation speed of yeast and human FG Nups by orders of magnitude. Aggregation can be inhibited by NTRs, providing a rationale on how the cell might control amyloid formation of FG Nups. The superb spatial resolving power of EM also reveals that hydrogels are enlaced amyloid fibres, and these findings have implications for existing transport models and for NPC assembly.