Figure 2.

Extracellular vesicle biogenesis and compositions. (a) Exosome biogenesis and intracellular life are depicted on the left. Cell surface proteins are endocytosed and trafficked to early endosomes. Once sorted to late endosomes, the endosomal sorting complex required for transport of (ESCRT)-0 complex recruits ubiquitinated proteins, while ESCRT-I and -II mediate the budding of intraluminal vesicles (ILVs). The multivesicular body (MVB) can either follow a degradation pathway fusing with lysosomes or proceed to release the ILV contents (as exosomes) to the extracellular space by an exocytic step. Microvesicle biogenesis via plasma membrane budding is illustrated on the right. Transmembrane proteins are clustered in discrete membrane domains that promote outward membrane budding. Tetraspanins and other proteins abundant at the domain may have a role by promoting the sorting of other components. Lipid-anchored (myristoylation, palmitoylation) proteins accumulate proteins in the lumen as well as contribute to membrane curvature. Additional mechanisms of microvesicle formation include the calcium-activated scramblases, which randomize the distribution of lipids between the two faces of the plasma membrane. The cytoskeleton becomes looser, while cytosolic proteins and RNA molecules are sorted into microvesicles. The specific ATPase VPS4 mediates the disassembly of the spiral by pulling its end. (b) Representative structure of exosomes with cargos. Note that placenta alkaline phosphatase (PLAP) is a specific marker of placenta-derived EVs. ARFs, ADP ribosylation factors; CD, cluster of differentiation; ESCRT, endosomal sorting complex required for transport; LAMPs, lysosome-associated membrane glycoproteins; mRNA, messenger RNA; miRNA, microRNA; RABs, member of RAS superfamily of small G proteins; TfR, transferrin receptor.