TY - JOUR
T1 - ER membrane contact sites support endosomal small GTPase conversion for exosome secretion
AU - Verweij, Frederik J.
AU - Bebelman, Maarten P.
AU - George, Anna E.
AU - Couty, Mickael
AU - Bécot, Anaïs
AU - Palmulli, Roberta
AU - Heiligenstein, Xavier
AU - Sirés-Campos, Julia
AU - Raposo, Graça
AU - Pegtel, Dirk Michiel
AU - van Niel, Guillaume
N1 - Publisher Copyright: © 2022 Verweij et al.
PY - 2022/12/5
Y1 - 2022/12/5
N2 - 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 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.
AB - 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 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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U2 - https://doi.org/10.1083/jcb.202112032
DO - https://doi.org/10.1083/jcb.202112032
M3 - Article
C2 - 36136097
SN - 0021-9525
VL - 221
SP - 1
EP - 18
JO - The Journal of cell biology
JF - The Journal of cell biology
IS - 12
M1 - e202112032
ER -