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Nuclear envelope-associated endosomes deliver surface proteins to the nucleus

Endocytosis directs molecular cargo along three main routes: recycling to the cell surface, transport to the Golgi apparatus or degradation in endolysosomes. Pseudomonas exotoxin A (PE) is a bacterial protein that typically traffics to the Golgi and then the endoplasmic reticulum before translocatin...

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Autores principales: Chaumet, Alexandre, Wright, Graham D., Seet, Sze Hwee, Tham, Keit Min, Gounko, Natalia V., Bard, Frederic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579783/
https://www.ncbi.nlm.nih.gov/pubmed/26356418
http://dx.doi.org/10.1038/ncomms9218
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author Chaumet, Alexandre
Wright, Graham D.
Seet, Sze Hwee
Tham, Keit Min
Gounko, Natalia V.
Bard, Frederic
author_facet Chaumet, Alexandre
Wright, Graham D.
Seet, Sze Hwee
Tham, Keit Min
Gounko, Natalia V.
Bard, Frederic
author_sort Chaumet, Alexandre
collection PubMed
description Endocytosis directs molecular cargo along three main routes: recycling to the cell surface, transport to the Golgi apparatus or degradation in endolysosomes. Pseudomonas exotoxin A (PE) is a bacterial protein that typically traffics to the Golgi and then the endoplasmic reticulum before translocating to the cytosol. Here we show that a substantial fraction of internalized PE is also located in nuclear envelope-associated endosomes (NAE), which display limited mobility, exhibit a propensity to undergo fusion and readily discharge their contents into the nuclear envelope. Electron microscopy and protein trapping in the nucleus indicate that NAE mediate PE transfer into the nucleoplasm. RNAi screening further revealed that NAE-mediated transfer depends on the nuclear envelope proteins SUN1 and SUN2, as well as the Sec61 translocon complex. These data reveal a novel endosomal route from the cell surface to the nucleoplasm that facilitates the accumulation of extracellular and cell surface proteins in the nucleus.
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spelling pubmed-45797832015-10-01 Nuclear envelope-associated endosomes deliver surface proteins to the nucleus Chaumet, Alexandre Wright, Graham D. Seet, Sze Hwee Tham, Keit Min Gounko, Natalia V. Bard, Frederic Nat Commun Article Endocytosis directs molecular cargo along three main routes: recycling to the cell surface, transport to the Golgi apparatus or degradation in endolysosomes. Pseudomonas exotoxin A (PE) is a bacterial protein that typically traffics to the Golgi and then the endoplasmic reticulum before translocating to the cytosol. Here we show that a substantial fraction of internalized PE is also located in nuclear envelope-associated endosomes (NAE), which display limited mobility, exhibit a propensity to undergo fusion and readily discharge their contents into the nuclear envelope. Electron microscopy and protein trapping in the nucleus indicate that NAE mediate PE transfer into the nucleoplasm. RNAi screening further revealed that NAE-mediated transfer depends on the nuclear envelope proteins SUN1 and SUN2, as well as the Sec61 translocon complex. These data reveal a novel endosomal route from the cell surface to the nucleoplasm that facilitates the accumulation of extracellular and cell surface proteins in the nucleus. Nature Pub. Group 2015-09-10 /pmc/articles/PMC4579783/ /pubmed/26356418 http://dx.doi.org/10.1038/ncomms9218 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chaumet, Alexandre
Wright, Graham D.
Seet, Sze Hwee
Tham, Keit Min
Gounko, Natalia V.
Bard, Frederic
Nuclear envelope-associated endosomes deliver surface proteins to the nucleus
title Nuclear envelope-associated endosomes deliver surface proteins to the nucleus
title_full Nuclear envelope-associated endosomes deliver surface proteins to the nucleus
title_fullStr Nuclear envelope-associated endosomes deliver surface proteins to the nucleus
title_full_unstemmed Nuclear envelope-associated endosomes deliver surface proteins to the nucleus
title_short Nuclear envelope-associated endosomes deliver surface proteins to the nucleus
title_sort nuclear envelope-associated endosomes deliver surface proteins to the nucleus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579783/
https://www.ncbi.nlm.nih.gov/pubmed/26356418
http://dx.doi.org/10.1038/ncomms9218
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