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Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9

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  • Mathilde Mathieu

    (INSERM U932, Institut Curie Centre de Recherche, PSL Research University
    Université de Paris)

  • Nathalie Névo

    (INSERM U932, Institut Curie Centre de Recherche, PSL Research University)

  • Mabel Jouve

    (CNRS UMR3215, Institut Curie, PSL Research University)

  • José Ignacio Valenzuela

    (CNRS UMR144, Institut Curie, PSL Research University)

  • Mathieu Maurin

    (INSERM U932, Institut Curie Centre de Recherche, PSL Research University)

  • Frederik J. Verweij

    (Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266)

  • Roberta Palmulli

    (Université de Paris
    CNRS UMR144, Institut Curie, PSL Research University)

  • Danielle Lankar

    (INSERM U932, Institut Curie Centre de Recherche, PSL Research University)

  • Florent Dingli

    (Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique)

  • Damarys Loew

    (Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique)

  • Eric Rubinstein

    (Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris)

  • Gaëlle Boncompain

    (CNRS UMR144, Institut Curie, PSL Research University)

  • Franck Perez

    (CNRS UMR144, Institut Curie, PSL Research University)

  • Clotilde Théry

    (INSERM U932, Institut Curie Centre de Recherche, PSL Research University)

Abstract

Despite their roles in intercellular communications, the different populations of extracellular vesicles (EVs) and their secretion mechanisms are not fully characterized: how and to what extent EVs form as intraluminal vesicles of endocytic compartments (exosomes), or at the plasma membrane (PM) (ectosomes) remains unclear. Here we follow intracellular trafficking of the EV markers CD9 and CD63 from the endoplasmic reticulum to their residency compartment, respectively PM and late endosomes. We observe transient co-localization at both places, before they finally segregate. CD9 and a mutant CD63 stabilized at the PM are more abundantly released in EVs than CD63. Thus, in HeLa cells, ectosomes are more prominent than exosomes. By comparative proteomic analysis and differential response to neutralization of endosomal pH, we identify a few surface proteins likely specific of either exosomes (LAMP1) or ectosomes (BSG, SLC3A2). Our work sets the path for molecular and functional discrimination of exosomes and small ectosomes in any cell type.

Suggested Citation

  • Mathilde Mathieu & Nathalie Névo & Mabel Jouve & José Ignacio Valenzuela & Mathieu Maurin & Frederik J. Verweij & Roberta Palmulli & Danielle Lankar & Florent Dingli & Damarys Loew & Eric Rubinstein &, 2021. "Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24384-2
    DOI: 10.1038/s41467-021-24384-2
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    Cited by:

    1. Bárbara Adem & Nuno Bastos & Carolina F. Ruivo & Sara Sousa-Alves & Carolina Dias & Patrícia F. Vieira & Inês A. Batista & Bruno Cavadas & Dieter Saur & José C. Machado & Dawen Cai & Sonia A. Melo, 2024. "Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    2. Hayden Weng Siong Tan & Guang Lu & Han Dong & Yik-Lam Cho & Auginia Natalia & Liming Wang & Charlene Chan & Dennis Kappei & Reshma Taneja & Shuo-Chien Ling & Huilin Shao & Shih-Yin Tsai & Wen-Xing Din, 2022. "A degradative to secretory autophagy switch mediates mitochondria clearance in the absence of the mATG8-conjugation machinery," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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