Fig. 1. Biogenesis and uptake of exosomes in target cells.

(a) Early endosomes mature into late endosomes and exosomes are formed by a process of inward budding from the limiting membrane. Via this mechanism, cytoplasmic RNA molecules and functional proteins are encapsulated into exosomes. Moreover, transmembrane proteins maintain the same orientation relative to the cytoplasm and plasma membrane. In a second step, multivesicular endosomes fuse with the cellular membrane to release the exosomes into the extracellular space. Several cellular signals have been suggested: (b) juxtracrine signaling through receptor-ligand interactions, (c) fusion of exosomes with the cellular membrane of the target cell, resulting in a direct release of the cargo into the cytoplasm, (d) phagocytosis in an actin-cytoskeletal and phosphatidylinositol 3-kinase dependent manner.