Figure 2.

Pathways of EV biogenesis and action. Three type of EVs are produced by most cells. Exosome biogenesis is initiated by the involution and pinching off of the endosomal membrane resulting in the production of an ILV that contains cytoplasmic constituents. As ILVs accumulate, MVBs are generated, which are then either degraded via the lysosomal pathway or trafficked to the cell surface whereupon they fuse with plasma membrane and liberate their contents, now becoming exosomes, into the extracellular space. Mircovesicles also contain similar cytoplasmic constituents but are generated by fission of the plasma membrane. Apoptotic bodies contain components of cell degradation and form by cytoplasmic bulging and separation from the cell as a result of cytosketetal breakdown during cell disassembly. Microvesicles and exosomes may bind to ECM components in the interstitial space or may be internalized by target cells, either by fusion with the plasma membrane or by endocytosis, both of which result in delivery of their respective molecular payloads into the recipient cell. Once released into the extracellular space, EVs may alternatively be carried in interstitial fluids into the main body fluids allowing them to target cells at distant sites or to be cleared.