Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2

Rania Ghossoub, Frédérique Lembo, Aude Rubio, Carole Baron Gaillard, Jérôme Bouchet, Nicolas Vitale, Josef Slavík, Miroslav Machala and Pascale Zimmermann ()
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Rania Ghossoub: Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068-CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes
Frédérique Lembo: Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068-CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes
Aude Rubio: Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068-CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes
Carole Baron Gaillard: Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068-CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes
Jérôme Bouchet: Institut Pasteur, Lymphocyte Cell Biology Unit
Nicolas Vitale: Institut des Neurosciences Cellulaires et Intégratives, UPR-3212, Centre National de la Recherche Scientifique, and Université de Strasbourg
Josef Slavík: Veterinary Research Institute
Miroslav Machala: Veterinary Research Institute
Pascale Zimmermann: Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068-CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract Exosomes are small vesicles that are secreted by cells and act as mediators of cell to cell communication. Because of their potential therapeutic significance, important efforts are being made towards characterizing exosomal contents. However, little is known about the mechanisms that govern exosome biogenesis. We have recently shown that the exosomal protein syntenin supports exosome production. Here we identify the small GTPase ADP ribosylation factor 6 (ARF6) and its effector phospholipase D2 (PLD2) as regulators of syntenin exosomes. ARF6 and PLD2 affect exosomes by controlling the budding of intraluminal vesicles (ILVs) into multivesicular bodies (MVBs). ARF6 also controls epidermal growth factor receptor degradation, suggesting a role in degradative MVBs. Yet ARF6 does not affect HIV-1 budding, excluding general effects on Endosomal Sorting Complexes Required for Transport. Our study highlights a novel pathway controlling ILV budding and exosome biogenesis and identifies an unexpected role for ARF6 in late endosomal trafficking.

Date: 2014
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DOI: 10.1038/ncomms4477

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