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Simple rules for passive diffusion through the nuclear pore complex

Open access
Timney, Benjamin L., Raveh, Barak, Mironska, Roxana, Trivedi, Jill M., Kim, Seung Joong, Russel, Daniel, Wente, Susan R., Sali, Andrej, Rout, Michael P.·2016·Journal of Cell Biology

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.

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Metadata

Authors
Timney, B. L., Raveh, B., Mironska, R., Trivedi, J. M., Kim, S. J., Russel, D., Wente, S. R., Sali, A., & Rout, M. P.
Venue
Journal of Cell Biology
Published
2016-10-03
Volume
215
Issue
1
Pages
57-76
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W2529120786
Cited by
457
References
4
FWCI
16.25
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Simple rules for passive diffusion through the nuclear pore complex. https://app.cochat.ai/papers/10.1083/jcb.201601004
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Timney, B. L., Raveh, B., Mironska, R., Trivedi, J. M., Kim, S. J., Russel, D., Wente, S. R., Sali, A., & Rout, M. P. (2016). Simple rules for passive diffusion through the nuclear pore complex. Journal of Cell Biology. https://doi.org/10.1083/jcb.201601004

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