Figure 1.

Exosomes biogenesis and composition. Exosomes biogenesis is based on a process of double invagination of the plasma membrane. The first step leading to the invagination process results into de novo formation of an early-sorting endosome characterized by cell-surface proteins and soluble proteins. Following the continuous exchange (import and export) of specific proteins and molecules from endosomes and mitochondria as well as with Trans Golgi network, the early-sorting endosome can mature into a late-sorting endosome through a second invagination of the plasma membrane leading to the generation of the Multi Vesicular Bodies (MVBs) composed by multiple intraluminal vesicles (ILVs). Then, MVBs can: (i) fuse with lysosomes resulting in the digestion of their ILVs or (ii) fuse with the plasma membrane thus leading to the release of ILVs as exosomes (22, 23). Exosomes expose several membrane proteins, such as tetraspanins (CD9, CD81, CD63) (24–28) and MHC molecules, both class I and class II, as well as Annexin and Flotillin. Moreover, exosomes content is highly variable depending on the cell of origin, but usually they contain cytoskeleton proteins (e.g., actin and tubulin), heat shock proteins such as HSP70 and HSP90, proteins associated to metabolism (GAPDH) (29–31), as well as specific proteins (e.g., ALIX, TSG101 and RAB proteins). Exosomes also contains different RNA species such as microRNAs, among which the most reported are miR-126-3p and miR-223-3p (32–36).