Syntenin-knock out reduces exosome turnover and viral transduction

Abstract

Exosomal transfers represent an important mode of intercellular communication. Syntenin is a small scaffold protein that, when binding ALIX, can direct endocytosed syndecans and syndecan cargo to budding endosomal membranes, supporting the formation of intraluminal vesicles that compose the source of a major class of exosomes. Syntenin, however, can also support the recycling of these same components to the cell surface. Here, by studying mice and cells with syntenin-knock out, we identify syntenin as part of dedicated machinery that integrates both the production and the uptake of secreted vesicles, supporting viral/exosomal exchanges. This study significantly extends the emerging role of heparan sulfate proteoglycans and syntenin as key components for macromolecular cargo internalization into cells.

Deliver on Time or Pay the Fine: Scheduling in Membrane Trafficking

“…Accordingly, depletion of CHMP4, an ESCRTIII subunit, reduces exosome production [112]. Notably, ESCRT-dependent exosome production is promoted by the Syntenin protein, which interacts with transmembrane receptors (i.e., Syndecan) and ALIX to increase receptor clusters and the generation of exosomes [112][113][114]. Among the sorting signals required for exosome production, the small integral membrane protein of the lysosome/late endosome (SIMPLE) is one of the most interesting [115].…”

In vivo imaging of EVs in zebrafish: New perspectives from “the waterside”

“…A first much needed development concerns the manipulation of EV-secretion in a tissue-specific manner in vivo. So far, several methods to manipulate EV secretion have been published, such as the use of chemical compounds affecting EV-biogenesis and/or -release, including Bafilomycin A1 and GW4869, or the interference with proteins crucial for EV biogenesis, such as Syntenin [88][89][90] . In a previous study in ZF, our group blocked EV secretion from the YSL in a tissue specific manner by using a Syntenin-a morpholino injected locally in the YSL.…”

“…So far, several methods to manipulate EV secretion have been published, such as the use of chemical compounds affecting EV‐biogenesis and/or ‐release, including Bafilomycin A1 and GW4869, or the interference with proteins crucial for EV biogenesis, such as syntenin. 88 , 89 , 90 In a previous study in ZF, our group blocked EV secretion from the YSL in a tissue‐specific manner by using a syntenin‐a morpholino injected locally in the YSL. This resulted in an impairment of CVP angiogenesis during ZF embryo development, suggesting a role for these EVs in vascular development and growth.…”

Tétraspanines et syndécanes

“…Les voies d'internalisation peuvent faire appel à des reconnaissances de type ligand-récepteur. Les syndécanes peuvent agir comme des récepteurs d'internalisation [14] et peuvent, entre autres, internaliser les vésicules extracellulaires [25,26]. D'un point de vue moléculaire, une absence de syndécanes à la membrane des cellules cibles pourrait être due à un défaut de recyclage dépendant de la synténine [26].…”

“…Les syndécanes peuvent agir comme des récepteurs d'internalisation [14] et peuvent, entre autres, internaliser les vésicules extracellulaires [25,26]. D'un point de vue moléculaire, une absence de syndécanes à la membrane des cellules cibles pourrait être due à un défaut de recyclage dépendant de la synténine [26]. Un déficit de chaînes d'héparanes sulfates des syndécanes peut également entraîner des défauts d'internalisation des exosomes [25].…”