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Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies

The rapid (<1 ms) transport of biological material to and from the cell nucleus is regulated by the nuclear pore complex (NPC). At the core of the NPC is a permeability barrier consisting of intrinsically disordered phenylalanine-glycine nucleoporins (FG Nups). Various types of nuclear transport...

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Autores principales: Davis, Luke K, Ford, Ian J, Hoogenboom, Bart W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880993/
https://www.ncbi.nlm.nih.gov/pubmed/35098921
http://dx.doi.org/10.7554/eLife.72627
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author Davis, Luke K
Ford, Ian J
Hoogenboom, Bart W
author_facet Davis, Luke K
Ford, Ian J
Hoogenboom, Bart W
author_sort Davis, Luke K
collection PubMed
description The rapid (<1 ms) transport of biological material to and from the cell nucleus is regulated by the nuclear pore complex (NPC). At the core of the NPC is a permeability barrier consisting of intrinsically disordered phenylalanine-glycine nucleoporins (FG Nups). Various types of nuclear transport receptors (NTRs) facilitate transport by partitioning in the FG Nup assembly, overcoming the barrier by their affinity to the FG Nups, and comprise a significant fraction of proteins in the NPC barrier. In previous work (Zahn et al., 2016), we revealed a universal physical behaviour in the experimentally observed binding of two well-characterised NTRs, Nuclear Transport Factor 2 (NTF2) and the larger Importin-β (Imp-β), to different planar assemblies of FG Nups, with the binding behaviour defined by negative cooperativity. This was further validated by a minimal physical model that treated the FG Nups as flexible homopolymers and the NTRs as uniformly cohesive spheres. Here, we build upon our original study by first parametrising our model to experimental data, and next predicting the effects of crowding by different types of NTRs. We show how varying the amounts of one type of NTR modulates how the other NTR penetrates the FG Nup assembly. Notably, at similar and physiologically relevant NTR concentrations, our model predicts demixed phases of NTF2 and Imp-β within the FG Nup assembly. The functional implication of NTR phase separation is that NPCs may sustain separate transport pathways that are determined by inter-NTR competition.
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spelling pubmed-88809932022-02-26 Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies Davis, Luke K Ford, Ian J Hoogenboom, Bart W eLife Physics of Living Systems The rapid (<1 ms) transport of biological material to and from the cell nucleus is regulated by the nuclear pore complex (NPC). At the core of the NPC is a permeability barrier consisting of intrinsically disordered phenylalanine-glycine nucleoporins (FG Nups). Various types of nuclear transport receptors (NTRs) facilitate transport by partitioning in the FG Nup assembly, overcoming the barrier by their affinity to the FG Nups, and comprise a significant fraction of proteins in the NPC barrier. In previous work (Zahn et al., 2016), we revealed a universal physical behaviour in the experimentally observed binding of two well-characterised NTRs, Nuclear Transport Factor 2 (NTF2) and the larger Importin-β (Imp-β), to different planar assemblies of FG Nups, with the binding behaviour defined by negative cooperativity. This was further validated by a minimal physical model that treated the FG Nups as flexible homopolymers and the NTRs as uniformly cohesive spheres. Here, we build upon our original study by first parametrising our model to experimental data, and next predicting the effects of crowding by different types of NTRs. We show how varying the amounts of one type of NTR modulates how the other NTR penetrates the FG Nup assembly. Notably, at similar and physiologically relevant NTR concentrations, our model predicts demixed phases of NTF2 and Imp-β within the FG Nup assembly. The functional implication of NTR phase separation is that NPCs may sustain separate transport pathways that are determined by inter-NTR competition. eLife Sciences Publications, Ltd 2022-01-31 /pmc/articles/PMC8880993/ /pubmed/35098921 http://dx.doi.org/10.7554/eLife.72627 Text en © 2022, Davis et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Physics of Living Systems
Davis, Luke K
Ford, Ian J
Hoogenboom, Bart W
Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies
title Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies
title_full Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies
title_fullStr Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies
title_full_unstemmed Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies
title_short Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies
title_sort crowding-induced phase separation of nuclear transport receptors in fg nucleoporin assemblies
topic Physics of Living Systems
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880993/
https://www.ncbi.nlm.nih.gov/pubmed/35098921
http://dx.doi.org/10.7554/eLife.72627
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AT hoogenboombartw crowdinginducedphaseseparationofnucleartransportreceptorsinfgnucleoporinassemblies