Biogenesis and Functions of Exosomes and Extracellular Vesicles

Research on extracellular vesicles (EVs) is a new and emerging field that is rapidly growing. Many features of these structures still need to be described and discovered. This concerns their biogenesis, their release and cellular entrance mechanisms, as well as their functions, particularly in vivo. Hence our knowledge on EV is constantly evolving and sometimes changing.

Biogenesis and secretion of exosomes, microvesicles, and microvesicle clusters


(a) Exosomes, 40–100 nm in diameter, are generated by formation of intraluminal vesicles (ILVs) in an ESCRT- or sphingomyelinase-dependent manner into an endosomal compartment or MVB. These structures can enter either the degradative or the secretory route. MVBs destined for exosome generation follow the secretory pathway, translocate to the cellular periphery where they fuse with the plasma membrane, and release their ILVs into the extracellular space. Once secreted, ILVs are termed exosomes. MVBs that enter the degradative pathway fuse with lysosomes where their cargo is degraded, a process of critical importance for the attenuation of signaling events. (b) Microvesicles, 100–1000 nm in diameter, are generated at the plasma membrane in a constitutive manner or upon stimuli. Nonsecretory exocytic vesicles (blue ) seem to release their vesicular content at the sites of microvesicle generation thereby contributing to the microvesicle biogenesis. In addition, membrane-remodeling events take place leading to the generation of a plasma membrane composition distinct from surrounding areas, but similar to those of exocytosed vesicles (red ). In the final stage, these areas bud off from the plasma membrane giving rise to secreted microvesicles. The mechanisms underlying the proposed membrane-remodeling or membrane-sorting events remain to be elucidated. (c) Microvesicle clusters are 5–800 nm in diameter consisting of smaller vesicle and tubules of about 60–80 nm in diameter. Prior to their secretion, microvesicles accumulate beneath the cell membrane where they bulge the plasma membrane until it ruptures releasing the microvesicle clusters. They remain coherent and attach as vesicle aggregate to the cell surface of bystander cells. PM plasma membrane, MC attachm. microvesicle cluster attachment.

Dreyer F, Baur A. (2016) Biogenesis and Functions of Exosomes and Extracellular Vesicles. Methods Mol Biol 1448:201-16. [abstract]

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