Journal
JOURNAL OF CELL BIOLOGY
Volume 221, Issue 3, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202108107
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Funding
- Biozentrum
- Swiss Nanoscience Institute
- Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) [310030_201062]
- National Science and Engineering Council of Canada (NSERC)
- Biozentrum PhD Fellowship Program
- Swiss National Science Foundation (SNF) [310030_201062] Funding Source: Swiss National Science Foundation (SNF)
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The selective barrier function of nuclear pore complexes (NPCs) relies on the interaction between phenylalanine-glycine nucleoporins (FG Nups) and karyopherins (Kaps) to discriminate nonspecific macromolecules. In vivo, different Kaps have varying impacts on the NPC barrier function.
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, importin beta 1/karyopherin beta 1 (Kap beta 1) 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 Kap beta 1 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.
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