Simple rules for passive diffusion through the nuclear pore complex

Benjamin L. Timney, Barak Raveh, Roxana Mironska, Jill M. Trivedi, Seung Joong Kim, Daniel Russel, Susan R. Wente, Andrej Sali, Michael P. Rout

Research output: Contribution to journalArticlepeer-review

271 Scopus citations

Abstract

Passive macromolecular diffusion through nuclear pore complexes (NPCs) is thought to decrease dramatically beyond a 30-60-kD size threshold. Using thousands of independent time-resolved fluorescence microscopy measurements in vivo, we show that the NPC lacks such a firm size threshold; instead, it forms a soft barrier to passive diffusion that intensifies gradually with increasing molecular mass in both the wild-type and mutant strains with various subsets of phenylalanine-glycine (FG) domains and different levels of baseline passive permeability. Brownian dynamics simulations replicate these findings and indicate that the soft barrier results from the highly dynamic FG repeat domains and the diffusing macromolecules mutually constraining and competing for available volume in the interior of the NPC, setting up entropic repulsion forces. We found that FG domains with exceptionally high net charge and low hydropathy near the cytoplasmic end of the central channel contribute more strongly to obstruction of passive diffusion than to facilitated transport, revealing a compartmentalized functional arrangement within the NPC.

Original languageAmerican English
Article number57
JournalJournal of Cell Biology
Volume215
Issue number1
DOIs
StatePublished - 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Timney et al.

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