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J Cell Biol. 2016 Oct 10;215(1):57-76. Epub 2016 Oct 3.

Simple rules for passive diffusion through the nuclear pore complex.

Author information

1
Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065.
2
Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158 Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158.
3
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.
4
Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158 Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158 sali@salilab.org rout@rockefeller.edu.
5
Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065 sali@salilab.org rout@rockefeller.edu.

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.

PMID:
27697925
PMCID:
PMC5057280
DOI:
10.1083/jcb.201601004
[Indexed for MEDLINE]
Free PMC Article

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