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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...

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Autores principales: Yoo, Tae Yeon, Mitchison, Timothy J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
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.
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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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