Importin-β modulates the permeability of the nuclear pore complex in a Ran-dependent manner
- University College London and Birkbeck College, United Kingdom
- Stanford University, United States
- University of California, Berkeley, United States
- École polytechnique fédérale de Lausanne, Switzerland
- 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.
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© 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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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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