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

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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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Alan R Lowe

Institute for Structural and Molecular Biology, University College London and Birkbeck College, London, United Kingdom

Competing interests
No competing interests declared.
Jeffrey H Tang

Department of Bioengineering, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Jaime Yassif

Department of Physics, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Michael Graf

Section of Life Sciences and Technologies, École polytechnique fédérale de Lausanne, Lausanne, Switzerland

Competing interests
No competing interests declared.
William Y C Huang

Department of Chemistry, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Jay T Groves

QB3, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Karsten Weis

Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, United States

Competing interests
Karsten Weis, Reviewing editor, eLife.
Jan T Liphardt

Department of Bioengineering, Stanford University, Stanford, United States

For correspondence
jan.liphardt@stanford.edu

Competing interests
No competing interests declared.

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