Exosomes are small vesicles that are secreted from cells to dispose of undegraded materials and mediate intercellular communication. A major source of exosomes is intraluminal vesicles within multivesicular endosomes that undergo exocytic fusion with the plasma membrane. An alternative fate of multivesicular endosomes is fusion with lysosomes, resulting in degradation of the intraluminal vesicles. The factors that determine whether multivesicular endosomes fuse with the plasma membrane or with lysosomes are unknown. In this study, we show that impairment of endolysosomal fusion by disruption of a pathway involving the BLOC-one-related complex (BORC), the small GTPase ARL8, and the tethering factor HOPS increases exosome secretion by preventing the delivery of intraluminal vesicles to lysosomes. These findings demonstrate that endolysosomal fusion is a critical determinant of the amount of exosome secretion and suggest that suppression of the BORC–ARL8–HOPS pathway could be used to boost exosome yields in biotechnology applications.
Inhibition of endolysosome fusion increases exosome secretion
Disclosures: The authors declare no competing interests exist.
- Award Id(s): ZIA HD001607
- Award Id(s): No 754412
Ganesh Vilas Shelke, Chad D. Williamson, Michal Jarnik, Juan S. Bonifacino; Inhibition of endolysosome fusion increases exosome secretion. J Cell Biol 5 June 2023; 222 (6): e202209084. doi: https://doi.org/10.1083/jcb.202209084
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