Fig. 1

Schematic diagram of the main production and uptake mechanism of exosomes. a. The formation of exosomes. Endocytosis encapsulates the substances to form an early endosome that continue to mature into MVBs containing ILVs. (I) ESCRT-dependent pathway: (1) Ubiquitinated cargo activates nearby ECSRT0 to recruit more cargos to the vicinity. (2) Activated ESCRT0 further activates downstream ESCRTI and ESCRTII to form a large polymeric complex that further closes the lipid membrane invagination. (3) ESCRTII then induces the activation and polymerization CHMP4 subunit of ESCRTIII, which can lead to the formation of ILV. (4) The formation of ILV activates the nearby Vps-4 complex to dissociate CHMP4 from the lipid membrane into recycling. (II) ESCRT-independent pathway: (1) Cargo located close to the endosome lipid membrane enters the lipid membrane microdomains enriched in ceramide. (2) Cargo is enveloped in the invaginated pocket with the assistance of various tetraspanins, transmembrane proteins and lipids and (3) eventually forms ILV. MVB containing ILVs is transported to the vicinity of lysosome for degradation. MVB can also be delivered to the vicinity of specific plasma membrane, and anchor and fuse to the plasma membrane to secret the ILVs to form exosomes. b. Association and uptake of exosomes. (I) Exosomes can recognize and bind to the recipient cells and transmit specific signals. (II) Exosomes enter target cells by clathrin-dependent endocytosis. (III) Exosomes enter target cells by clathrin-independent macropinocytosis or phagocytosis pathway. (IV) Exosomes enter cells by lipid rafts, such as caveolae, mediated endocytosis. Depending on the needs of the cells, the exosomal contents are released into the cytosol, the exosomes are transported to the lysosome for degradation and digestion, or the exosomes fuse with cell membrane again and are released to accomplish the transcellular transport