Facilitated aggregation of FG nucleoporins under molecular crowding conditions

EMBO Rep. 2013 Feb;14(2):178-83. doi: 10.1038/embor.2012.204. Epub 2012 Dec 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / chemistry*
  • Amyloid / ultrastructure
  • Dextrans / chemistry
  • Humans
  • Hydrogels / chemistry
  • Kinetics
  • Nuclear Pore Complex Proteins / chemistry*
  • Nuclear Pore Complex Proteins / ultrastructure
  • Osmolar Concentration
  • Porosity
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • beta Karyopherins / chemistry

Substances

  • Amyloid
  • Dextrans
  • Hydrogels
  • NUP153 protein, human
  • Nuclear Pore Complex Proteins
  • beta Karyopherins