Nuclear envelope-associated endosomes deliver surface proteins to the nucleus

Alexandre Chaumet, Graham D. Wright, Sze Hwee Seet, Keit Min Tham, Natalia V. Gounko and Frederic Bard ()
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Alexandre Chaumet: Institute of Molecular and Cell Biology
Graham D. Wright: Institute of Medical Biology
Sze Hwee Seet: Institute of Molecular and Cell Biology
Keit Min Tham: Institute of Molecular and Cell Biology
Natalia V. Gounko: Institute of Molecular and Cell Biology
Frederic Bard: Institute of Molecular and Cell Biology

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9218

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