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O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport
Macromolecular transport across the nuclear envelope depends on facilitated diffusion through nuclear pore complexes (NPCs). The interior of NPCs contains a permeability barrier made of phenylalanine-glycine (FG) repeat domains that selectively facilitates the permeation of cargoes bound to nuclear...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091080/ https://www.ncbi.nlm.nih.gov/pubmed/33909044 http://dx.doi.org/10.1083/jcb.202010141 |
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author | Yoo, Tae Yeon Mitchison, Timothy J. |
author_facet | Yoo, Tae Yeon Mitchison, Timothy J. |
author_sort | Yoo, Tae Yeon |
collection | PubMed |
description | Macromolecular transport across the nuclear envelope depends on facilitated diffusion through nuclear pore complexes (NPCs). The interior of NPCs contains a permeability barrier made of phenylalanine-glycine (FG) repeat domains that selectively facilitates the permeation of cargoes bound to nuclear transport receptors (NTRs). FG-repeat domains in NPCs are a major site of O-linked N-acetylglucosamine (O-GlcNAc) modification, but the functional role of this modification in nucleocytoplasmic transport is unclear. We developed high-throughput assays based on optogenetic probes to quantify the kinetics of nuclear import and export in living human cells. We found that increasing O-GlcNAc modification of the NPC accelerated NTR-facilitated transport of proteins in both directions, and decreasing modification slowed transport. Superresolution imaging revealed strong enrichment of O-GlcNAc at the FG-repeat barrier. O-GlcNAc modification also accelerated passive permeation of a small, inert protein through NPCs. We conclude that O-GlcNAc modification accelerates nucleocytoplasmic transport by enhancing the nonspecific permeability of the FG-repeat barrier, perhaps by steric inhibition of interactions between FG repeats. |
format | Online Article Text |
id | pubmed-8091080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80910802022-01-05 O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport Yoo, Tae Yeon Mitchison, Timothy J. J Cell Biol Report Macromolecular transport across the nuclear envelope depends on facilitated diffusion through nuclear pore complexes (NPCs). The interior of NPCs contains a permeability barrier made of phenylalanine-glycine (FG) repeat domains that selectively facilitates the permeation of cargoes bound to nuclear transport receptors (NTRs). FG-repeat domains in NPCs are a major site of O-linked N-acetylglucosamine (O-GlcNAc) modification, but the functional role of this modification in nucleocytoplasmic transport is unclear. We developed high-throughput assays based on optogenetic probes to quantify the kinetics of nuclear import and export in living human cells. We found that increasing O-GlcNAc modification of the NPC accelerated NTR-facilitated transport of proteins in both directions, and decreasing modification slowed transport. Superresolution imaging revealed strong enrichment of O-GlcNAc at the FG-repeat barrier. O-GlcNAc modification also accelerated passive permeation of a small, inert protein through NPCs. We conclude that O-GlcNAc modification accelerates nucleocytoplasmic transport by enhancing the nonspecific permeability of the FG-repeat barrier, perhaps by steric inhibition of interactions between FG repeats. Rockefeller University Press 2021-04-28 /pmc/articles/PMC8091080/ /pubmed/33909044 http://dx.doi.org/10.1083/jcb.202010141 Text en © 2021 Yoo and Mitchison http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Report Yoo, Tae Yeon Mitchison, Timothy J. O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport |
title | O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport |
title_full | O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport |
title_fullStr | O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport |
title_full_unstemmed | O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport |
title_short | O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport |
title_sort | o-glcnac modification of nuclear pore complexes accelerates bidirectional transport |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091080/ https://www.ncbi.nlm.nih.gov/pubmed/33909044 http://dx.doi.org/10.1083/jcb.202010141 |
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