ER Membrane Contact Sites support endosomal small GTPase conversion for exosome secretion
Verweij, Frederik; Bebelman, Maarten P; George, Anna; Couty, Mickael; Bécot, Anaïs; Palmulli, Roberta; Heiligenstein, Xavier; Sires-Campos, Julia; Raposo, Graca; Pegtel, Dirk Michiel; Van Niel, Guillaume
(2022) Journal of Cell Biology, volume 221, issue 12, pp. 1 - 18
(Article)
Abstract
Exosomes are endosome-derived extracellular vesicles involved in intercellular communication. They are generated as intraluminal vesicles within endosomal compartments that fuse with the plasma membrane (PM). The molecular events that generate secretory endosomes and lead to the release of exosomes are not well understood. We identified a subclass of non-proteolytic endosomes
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at prelysosomal stage as the compartment of origin of CD63 positive exosomes. These compartments undergo a Rab7a/Arl8b/Rab27a GTPase cascade to fuse with the PM. Dynamic endoplasmic reticulum (ER)-late endosome (LE) membrane contact sites (MCS) through ORP1L have the distinct capacity to modulate this process by affecting LE motility, maturation state, and small GTPase association. Thus, exosome secretion is a multi-step process regulated by GTPase switching and MCS, highlighting the ER as a new player in exosome-mediated intercellular communication.
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Keywords: Biological Transport, Cell Communication, Cell Membrane/metabolism, Endoplasmic Reticulum/metabolism, Endosomes/enzymology, Exosomes/metabolism, rab GTP-Binding Proteins/metabolism
ISSN: 0021-9525
Publisher: Rockefeller University Press
Note: Funding Information: This article was funded by a European Molecular Biology Organization grant (EMBO ALTF 1383-2014), a Fondation ARC pour la Recherche sur le Cancer fellowship (PJA 20161204808), and a Dutch Cancer Fund (KWF-YIG 12849) to F.J. Verweij, a Dutch Organizations for Scientific Research–Amsterdam Institute for Molecules, Medicines, and Systems STAR Graduate Program grant (022.005.031) and a Cancer Center Amsterdam travel grant to M.P. Bebelman, a Dutch Cancer Fund (KWF-5510) and a Cancer Center Amsterdam–VU University Medical Center grant to D.M. Pegtel, and a Fondation pour la Recherche Médicale grant (AJE20160635884) to G. van Niel and an Institut National Du Cancer grant (INCA N°2019-125 PLBIO19-059) to F.J. Verweij and G. van Niel. The Nikon Imaging Centre at In-stitut Curie is member of the French National Research Infrastructure France-BioImaging (ANR10-INBS-04). The authors declare no competing financial interests. Publisher Copyright: © 2022 Verweij et al.
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