Fig. 1: Exosome biogenesis.
(a) Exosomes form in MVBs through three primary pathways: (1) ESCRTs involve four complexes, ESCRT-0, -I, -II, and -III. ESCRT-0 and -I recruit cargos and ESCRT-II, which then recruits ESCRT-III. ESCRT-III promotes ILV budding. (2) Tetraspanins cluster membrane cargos and reside at membrane domains that promote ILV budding. (3) Ceramide and cholesterol lipid domains recruit factors, including flotillins and the autophagy-related protein LC3. Flotillins recruit Rab31, promoting enrichment of EGFR in CD63-containing MVBs. (b) MVBs fuse with lysosomes for degradation. (c) Decreased Rab7 activity due to TBC1D2B recruitment by Rab31 or impaired lysosomal acidification may block MVB–lysosome fusion. (d) Rab27 promotes fusion of MVBs with the plasma membrane. (e) ILVs are secreted as a heterogeneous mixture of exosomes.
