Facilitated aggregation of FG nucleoporins under molecular crowding conditions. (14th December 2012)

• Record Type: Journal Article
• Authors: Milles, Sigrid; Huy Bui, Khanh; Koehler, Christine; Eltsov, Mikhail; Beck, Martin; Lemke, Edward A
• Is Part Of: EMBO reports. Volume 14:Number 2(2013)
• Page Start: 178
• Page End: 183
• Publication Date: 2012-12-14
• Subjects: intrinsically disordered protein -- amyloid fibres -- electron microscopy -- fluorescence spectroscopy -- nuclear pore complex; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.1038/embor.2012.204
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract : 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. Facilitated aggregation of FG nucleoporins under molecular crowding conditions: Intrinsically disordered FG‐nucleoporins that form the permeability barrier of the nuclear pore complex aggregate rapidly under molecular crowding conditions and form amyloid fibres that can also interlace into hydrogels at high protein concentrations. Nuclear transport receptors inhibit FG‐nucleoporin aggregation.