Biogenesis and secretion of exosomes

Abstract

Although observed for several decades, the release of membrane-enclosed vesicles by cells into their surrounding environment has been the subject of increasing interest in the past few years, which led to the creation, in 2012, of a scientific society dedicated to the subject: the International Society for Extracellular Vesicles. Convincing evidence that vesicles allow exchange of complex information fuelled this rise in interest. But it has also become clear that different types of secreted vesicles co-exist, with different intracellular origins and modes of formation, and thus probably different compositions and functions. Exosomes are one sub-type of secreted vesicles. They form inside eukaryotic cells in multivesicular compartments, and are secreted when these compartments fuse with the plasma membrane. Interestingly, different families of molecules have been shown to allow intracellular formation of exosomes and their subsequent secretion, which suggests that even among exosomes different sub-types exist.

Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes

“…Although several intracellular proteins (e.g., of the RAB, ESCRT, or SNARE families) have already been described as required for "exosome" biogenesis and secretion (reviewed in ref. 7), the effect of these machineries on secretion of the other EV subtypes was in most cases not investigated. We propose that any new drug, gene-inhibiting tool, or treatment claiming specific effects on a population of secreted EVs (especially on exosomes) should be systematically tested for its effects on other EVs.…”

“…Some EVs are directly formed and released from the cells' plasma membrane (PM), and are often called microparticles, (shed) microvesicles, or ectosomes: these EVs display sizes ranging from a few dozens of nanometers to a few micrometers. Internal vesicles generated within multivesicular endosomal compartments (MVB) are secreted when these compartments fuse with the PM, thus releasing their internal vesicles in the extracellular milieu: these EVs are termed exosomes (3,7). Exosomes are classically defined by their size, similar to the size of intraluminal vesicles of MVBs (i.e., below 150 nm in diameter), and their content of endosome-associated proteins.…”

Extracellular vesicles and viruses: Are they close relatives?

“…Moreover, EV-associated miRNAs and mRNAs have been found to be enriched in certain sorting motifs (14)(15)(16). Recent scientific breakthroughs have shown that EV-associated proteins, lipids, and genetic material can be functionally transferred to target cells (13,(17)(18)(19), strongly implying that EVs and (retro) viruses have in common not only structural but also some functional aspects. This similarity is a reflection of the similarity in biogenesis of EVs and viruses (Fig.…”

Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer

“…MVBs can be either fused with lysosomes or with the plasma membrane, which allows the release of their content to the extracellular compartment [35]. Exosomes then will interact with recipient target cells via different mechanisms such as plasma membrane fusion and transport (RAB11, RAB27 and RAB35) or adhesion to corresponding receptors [36,37].…”