Fig. 1

The generation of Exo is regulated by multiple intracellular pathways. Cargoes are sequestrated into early endosomes which are originated from endocytosis (Rab4, Rab5, Rab7, and Rab35) or Trans-Golgi network (Rab11). Exo fusion and recycling back pathways are regulated by the activity of Rab proteins (Rab 27a and Rab27b), SNARE complex (SYX-5, YKT6, VAMP3.7, SNAP23). The formation of ILVs inside the MVBs is mediated by inward invagination endosomal membrane via multiple pathways: ESCRT-dependent (ESCRT-0, I, II, II and syndecan-syntenin-ALIX axis), and ESCRT-independent pathways (ceramide-enriched microdomains and tetraspanin-enriched microdomains). Multiple pathways can distinguish the orientation of MVBs toward lysosomal depredation or fusion with the plasma membrane. ISGylation process can induce lysosomal degradation. The lysosomal degradation pathway is regulated by interaction Rab7 with Dynein and induction mobility toward microtubule minus ends. To fuse the MVBs with the membrane, various Rab-GTPases control the transport of MVBs on microtubules. Rab27 stabilizes the rearrangement of the actin cytoskeleton by improving the attachment of Cortactin, leading to MVBs docking. Docking, tethering, and releasing are three steps. The activity of SNAREs mediates the fusion of the MVB membrane with the plasma membrane