The Nucleoporin Nup358/RanBP2 Promotes Nuclear Import in a Cargo- and Transport Receptor-Specific Manner

Authors

  • Sarah Wälde,

    1. Department of Biochemistry I, Faculty of Medicine, Georg-August-University of Göttingen, Göttingen, Germany
    2. Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA
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  • Ketan Thakar,

    1. Department of Biochemistry I, Faculty of Medicine, Georg-August-University of Göttingen, Göttingen, Germany
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    • These authors contributed equally to the work.

  • Saskia Hutten,

    1. Department of Biochemistry I, Faculty of Medicine, Georg-August-University of Göttingen, Göttingen, Germany
    2. Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, UK
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    • These authors contributed equally to the work.

  • Christiane Spillner,

    1. Department of Biochemistry I, Faculty of Medicine, Georg-August-University of Göttingen, Göttingen, Germany
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  • Annegret Nath,

    1. Department of Biochemistry I, Faculty of Medicine, Georg-August-University of Göttingen, Göttingen, Germany
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  • Ulrich Rothbauer,

    1. LMU-BioCenter, Martinsried, Germany
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  • Stefan Wiemann,

    1. Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Ralph H. Kehlenbach

    Corresponding author
    • Department of Biochemistry I, Faculty of Medicine, Georg-August-University of Göttingen, Göttingen, Germany
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Corresponding author: Ralph H. Kehlenbach, rkehlen@gwdg.de

Abstract

In vertebrates, the nuclear pore complex (NPC), the gate for transport of macromolecules between the nucleus and the cytoplasm, consists of approximately 30 different nucleoporins (Nups). The Nup and SUMOE3-ligase Nup358/RanBP2 are the major components of the cytoplasmic filaments of the NPC. In this study, we perform a structure–function analysis of Nup358 and describe its role in nuclear import of specific proteins. In a screen for nuclear proteins that accumulate in the cytoplasm upon Nup358 depletion, we identified proteins that were able to interact with Nup358 in a receptor-independent manner. These included the importin α/β-cargo DBC-1 (deleted in breast cancer 1) and DMAP-1 (DNA methyltransferase 1 associated protein 1). Strikingly, a short N-terminal fragment of Nup358 was sufficient to promote import of DBC-1, whereas DMAP-1 required a larger portion of Nup358 for stimulated import. Neither the interaction of RanGAP with Nup358 nor its SUMO-E3 ligase activity was required for nuclear import of all tested cargos. Together, Nup358 functions as a cargo- and receptor-specific assembly platform, increasing the efficiency of nuclear import of proteins through various mechanisms.

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