Fig. 1

Overview of exosome biogenesis. a. Exosome biogenesis starts with the formation of endocytic vesicles, the process whereby the plasma membrane locally invaginates, and is regulated by proteins such as clathrin and caveolin. Endocytic vesicles fuse to form the early endosome, which matures towards MVBs, also known as late endosomes. This progression involves the inward budding of early endosomes, leading to the formation of MVBs that contain ILVs. b. During MVBs maturation, cargoes including proteins, RNA, and DNA are sorted into ILVs. These interactions enrich MVBs with components from multiple intracellular organelles and substances, which is fundamental for the functional heterogeneity of exosomes. c. The fate of MVBs has two potential outcomes: 1. MVBs may be transported to the plus end of microtubules (left) by motor proteins. Following the transport, MVBs bind to the cell membrane and release ILVs as exosomes under the regulation of the SNARE complex. 2. Alternatively, they can be transported towards the minus end of microtubules (right) by motor proteins, bind to lysosomes, and degrade subsequently. MVBs multivesicular bodies, ILV intraluminal vesicles, ER endoplasmic reticulum, TGN trans Golgi network, HOPS homotypic fusion and protein-sorting, Arl8b Rab7-to-Arf-like GTPase 8, SKIP SifA- and kinesin-interacting protein, RILP Rab7-interacting lysosomal protein, BORC BLOC one-related complex, SNARE soluble N-ethylmaleimide-sensitive fusion attachment protein receptor, RBP RNA-binding protein