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Cellular Proteases Prime Extracellular Vesicles for Intercellular Communication
Author(s) -
Qing Enya,
Hantak Michael,
Gallagher Tom
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb235
Subject(s) - proteases , microbiology and biotechnology , endosome , intracellular , biology , cytoplasm , lipid bilayer fusion , protease , chemistry , virus , virology , biochemistry , enzyme
Extracellular vesicles (EVs) can mediate intercellular communication by encasing cytoplasmic cargo and transferring this luminal material into nearby cells. This EV‐mediated transfer process is important for maintaining metazoan homeostasis (a positive effect) and is also implicated in metastatic tumor progression (a negative effect). To transfer cytoplasmic cargo, an EV must fuse its membrane with the plasma or endosomal cell membrane on a target cell. A poor understanding of this fusion process has hindered EV biology. We and others are impressed by the similarities between EVs and enveloped viruses. During enveloped virus infection, luminal cargos are transferred through an analogous fusion process. Activating viral membrane fusion frequently requires host proteases. Therefore, we hypothesized that cellular proteases prime EV‐mediated cargo transfers. We quantified EV cargo transfers with a membrane fusion‐dependent reporter complementation assay, where signals are generated only after EV‐mediated delivery of reporter (luciferase) proteins. We found that transmembrane protease serine 2 (TMPRSS2), a protease known to activate several viral fusion‐catalyzing enyzmes, profoundly increased EV‐mediated cargo transfers. TMPRSS2 mediated its effects within the cells producing EVs, suggesting the existence of a protease‐primed, virus‐like fusogen that traffics on EVs to prompt EV‐target cell coalescence and cargo delivery. Our findings may offer increased understanding of EVs and their roles in regulating crucial biological processes, and may provide tools to manipulate EVs for therapeutic purposes.