Nuclear envelope-associated endosomes deliver surface proteins to the nucleus
Chaumet, A Wright, G.D Seet, S.H Tham, K.M Gounko, N.V Bard, F
Chaumet, A
Wright, G.D
Seet, S.H
Tham, K.M
Gounko, N.V
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Alternative Title
Abstract
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. © 2015 Macmillan Publishers Limited. All rights reserved.
Keywords
cell surface protein, early endosome antigen 1, epidermal growth factor receptor, histone H1, membrane protein, nuclear protein, protein disulfide isomerase, Pseudomonas exotoxin, SUN1 protein, SUN2 protein, translocon, tubulin, unclassified drug, bacterial toxin, exotoxin, membrane protein, microtubule associated protein, nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase, nuclear localization signal, nuclear protein, SEC61A1 protein, human, signal peptide, SUN1 protein, human, SUN2 protein, human, toxA protein, Pseudomonas aeruginosa, translocon, virulence factor, bacterium, cell organelle, cells and cell components, mobility, protein, RNA, translocation, Article, cell fractionation, cell nucleus, cell nucleus membrane, cell surface, controlled study, cytolysis, cytosol, cytosolic fraction, electron microscopy, endosome, female, Golgi complex, HeLa cell line, human, human cell, immunoprecipitation, inner membrane, nuclear import, nuclear localization signal, nuclear pore, outer membrane, protein binding, protein localization, protein transport, regulatory mechanism, RNA interference, Western blotting, cell nucleus, cell nucleus membrane, confocal microscopy, endocytosis, endoplasmic reticulum, endosome, fluorescent antibody technique, gene silencing, genetics, metabolism, tumor cell line, Bacteria (microorganisms), Pseudomonas exotoxin, ADP Ribose Transferases, Bacterial Toxins, Cell Line, Tumor, Cell Nucleus, Cytosol, Endocytosis, Endoplasmic Reticulum, Endosomes, Exotoxins, Fluorescent Antibody Technique, Gene Knockdown Techniques, Golgi Apparatus, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Microscopy, Confocal, Microscopy, Electron, Microtubule-Associated Proteins, Nuclear Envelope, Nuclear Localization Signals, Nuclear Proteins, Protein Transport, SEC Translocation Channels, Virulence Factors
Source Title
Nature Communications
Publisher
Nature Publishing Group
Series/Report No.
Collections
Rights
Attribution 4.0 International
Date
2015
DOI
10.1038/ncomms9218
Type
Article