FIGURE 5.

Biogenesis, cargo loading, and secretion of exosomes. Invagination of the endocytic membrane leads to the creation of ILVs and finally to secretion of exosomes. In the course of the maturation process, cargo molecules (proteins, lipids, and RNAs) are loaded into ILVs via an ESCRT–dependent pathway or an ESCRT–independent pathway. Maturation of the initial endosomes results in the formation of MVBs that are transferred to the trans-Golgi network (TGN) in order to recycle the endosomes. The MVBs can also be delivered to the lysosomes for degradation, or moved along micro-tubules for fusion with the plasma membrane in order to release the exosomes into the extra-cellular space. Moreover, MVB fusion with the plasma membrane involves the SNARE and Rab GTPase complexes. Finally, exosomal contents originating from the source cells may be taken up by the target cells via a direct membrane fusion, receptor-ligand interactions, or by endocytosis,