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

Kalita, Joanna and Kapinos, Larisa E. and Zheng, Tiantian and Rencurel, Chantal and Zilman, Anton and Lim, Roderick Y. H.. (2022) Karyopherin enrichment and compensation fortifies the nuclear pore complex against nucleocytoplasmic leakage. Journal of Cell Biology, 221 (3). e202108107.

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Official URL: https://edoc.unibas.ch/87681/

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Nuclear pore complexes (NPCs) discriminate nonspecific 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 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, which enable CRM1 to compensate for the loss of Kapβ1 as a means to maintain NPC barrier function. However, such a compensatory mechanism is constrained by the cellular abundances and different binding kinetics for each respective Kap, as evidenced for importin-5. Consequently, we find that NPC malfunction and nucleocytoplasmic leakage result from poor Kap enrichment.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Nanobiology Argovia (Lim)
UniBasel Contributors:Lim, Roderick Y.H.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Rockefeller University Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Mar 2022 11:40
Deposited On:09 Mar 2022 11:40

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