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

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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
    Department of Human Genetics)

  • Jérôme Bouchet

    (Institut Pasteur, Lymphocyte Cell Biology Unit
    CNRS, URA-1961)

  • 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
    Department of Human Genetics)

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.

Suggested Citation

  • Rania Ghossoub & Frédérique Lembo & Aude Rubio & Carole Baron Gaillard & Jérôme Bouchet & Nicolas Vitale & Josef Slavík & Miroslav Machala & Pascale Zimmermann, 2014. "Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2," Nature Communications, Nature, vol. 5(1), pages 1-12, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4477
    DOI: 10.1038/ncomms4477
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    Cited by:

    1. Sarah Renaud & Anthony Lefebvre & Olivier Moralès & Nadira Delhem, 2019. "Mini Review - Exosomes from Discovery to Isolation," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 15(2), pages 11286-11293, February.

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