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Karyopherin enrichment and compensation fortifies the nuclear pore complex against nucleocytoplasmic leakage

ABSTRACT: Nuclear pore complexes (NPCs) discriminate non-specific macromolecules from importin and exportin receptors, collectively termed karyopherins (Kaps), that mediate nucleocytoplasmic transport. This selective barrier function is attributed to the behavior of intrinsically disordered phenylalanine-glycine nucleoporins (FG Nups) that guard the NPC channel. However, NPCs in vivo are typically enriched with different Kaps, and how they impact on the NPC barrier remains unknown. Here, we show that two major Kaps, importinβ1/karyopherinβ1 (Kapβ1) and exportin 1/chromosomal maintenance 1 (CRM1) are required to fortify NPC barrier function in vivo. Their enrichment at the NPC is sustained by promiscuous binding interactions with the FG Nups resulting in a compensatory mechanism that is constrained by their respective cellular abundances and different binding kinetics as evidenced for another Kap, Importin-5. Hence, Kapβ1 and CRM1 engage in a balancing act to reinforce NPC barrier function. Consequently, NPC malfunction and nucleocytoplasmic leakage result from poor Kap enrichment.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive HF

ORGANISM(S): Canis Familiaris (dog) (canis Lupus Familiaris)

TISSUE(S): Cell Culture

SUBMITTER: Alexander Schmidt

LAB HEAD: Alexander Schmidt

PROVIDER: PXD028074 | Pride | 2022-01-26

REPOSITORIES: Pride

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2018-05-22 | PXD008334 | Pride

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Pre-assembled Nuclear Pores Insert into the Nuclear Envelope During Early Development

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SILAC-Tp (12 importins)

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Nucleoporin Nup153 Regulates Stem Cell Pluripotency through Gene Silencing

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