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Updated: May 5, 2026

Single-Molecule Imaging of Nuclear Transport
Published on: June 10, 2010
Npap60/Nup50 is a tri-stable switch that stimulates importin-alpha:beta-mediated nuclear protein import
Mark E Lindsay1, Kendra Plafker, Alicia E Smith
1Center for Cell Signaling, Department of Microbiology, University of Virginia School of Medicine, Charlottesville 22908, USA.
Abstract:
Many nuclear-targeted proteins are transported through the nuclear pore complex (NPC) by the importin-alpha:beta receptor. We now show that Npap60 (also called Nup50), a protein previously believed to be a structural component of the NPC, is a Ran binding protein and a cofactor for importin-alpha:beta-mediated import. Npap60 is a tri-stable switch that alternates between binding modes. The C terminus binds importin-beta through RanGTP. The N terminus binds the C terminus of importin-alpha, while a central domain binds importin-beta. Npap60:importin-alpha:beta binds cargo and can stimulate nuclear import. Endogenous Npap60 can shuttle and is accessible from the cytoplasmic side of the nuclear envelope. These results identify Npap60 as a cofactor for importin-alpha:beta nuclear import and as a previously unidentified subunit of the importin complex.
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