Cell
Volume 150, Issue 4, 17 August 2012, Pages 738-751
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Article
The Permeability of Reconstituted Nuclear Pores Provides Direct Evidence for the Selective Phase Model

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Summary

Nuclear pore complexes (NPCs) maintain a permeability barrier between the nucleus and the cytoplasm through FG-repeat-containing nucleoporins (Nups). We previously proposed a “selective phase model” in which the FG repeats interact with one another to form a sieve-like barrier that can be locally disrupted by the binding of nuclear transport receptors (NTRs), but not by inert macromolecules, allowing selective passage of NTRs and associated cargo. Here, we provide direct evidence for this model in a physiological context. By using NPCs reconstituted from Xenopus laevis egg extracts, we show that Nup98 is essential for maintaining the permeability barrier. Specifically, the multivalent cohesion between FG repeats is required, including cohesive FG repeats close to the anchorage point to the NPC scaffold. Our data exclude alternative models that are based solely on an interaction between the FG repeats and NTRs and indicate that the barrier is formed by a sieve-like FG hydrogel.

Highlights

► A single FG Nup, Nup98, dominates the permeability barrier of vertebrate NPC ► Nup98 FG repeats are highly cohesive and form hydrogels of NPC-like permeability ► Nuclei with engineered NPCs reveal barrier-relevant features of FG repeat domain ► The NPC barrier requires multivalent cohesion between FG repeats

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