Importin-β modulates the permeability of the nuclear pore complex in a Ran-dependent manner

  1. Alan R Lowe
  2. Jeffrey H Tang
  3. Jaime Yassif
  4. Michael Graf
  5. William Y C Huang
  6. Jay T Groves
  7. Karsten Weis
  8. Jan T Liphardt  Is a corresponding author
  1. University College London and Birkbeck College, United Kingdom
  2. Stanford University, United States
  3. University of California, Berkeley, United States
  4. École polytechnique fédérale de Lausanne, Switzerland
  5. Howard Hughes Medical Institute, University of California, Berkeley, United States

Abstract

Soluble karyopherins of the importin-β (impβ) family use RanGTP to transport cargos directionally through the nuclear pore complex (NPC). Whether impβ or RanGTP regulate the permeability of the NPC itself has been unknown. Here, we identify a stable pool of impβ at the NPC. A subpopulation of this pool is rapidly turned-over by RanGTP, likely at Nup153. Impβ, but not transportin-1 (TRN1), alters the pore's permeability in a Ran-dependent manner, suggesting that impβ is a functional component of the NPC. Upon reduction of Nup153 levels, inert cargos more readily equilibrate across the NPC yet active transport is impaired. When purified impβ or TRN1 are mixed with Nup153 in vitro, higher-order, multivalent complexes form. RanGTP dissolves the impβ•Nup153 complexes but not those of TRN1•Nup153. We propose that impβ and Nup153 interact at the NPC's nuclear face to form a Ran-regulated mesh that modulates NPC permeability.

Article and author information

Author details

  1. Alan R Lowe

    Institute for Structural and Molecular Biology, University College London and Birkbeck College, London, United Kingdom
    Competing interests
    No competing interests declared.
  2. Jeffrey H Tang

    Department of Bioengineering, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  3. Jaime Yassif

    Department of Physics, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  4. Michael Graf

    Section of Life Sciences and Technologies, École polytechnique fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    No competing interests declared.
  5. William Y C Huang

    Department of Chemistry, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  6. Jay T Groves

    QB3, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  7. Karsten Weis

    Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    Karsten Weis, Reviewing editor, eLife.
  8. Jan T Liphardt

    Department of Bioengineering, Stanford University, Stanford, United States
    For correspondence
    jan.liphardt@stanford.edu
    Competing interests
    No competing interests declared.

Reviewing Editor

  1. Vivek Malhotra, Center for Genomic Regulation, Spain

Publication history

  1. Received: July 18, 2014
  2. Accepted: February 27, 2015
  3. Accepted Manuscript published: March 6, 2015 (version 1)
  4. Version of Record published: March 27, 2015 (version 2)

Copyright

© 2015, Lowe et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Alan R Lowe
  2. Jeffrey H Tang
  3. Jaime Yassif
  4. Michael Graf
  5. William Y C Huang
  6. Jay T Groves
  7. Karsten Weis
  8. Jan T Liphardt
(2015)
Importin-β modulates the permeability of the nuclear pore complex in a Ran-dependent manner
eLife 4:e04052.
https://doi.org/10.7554/eLife.04052

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