Fig. 1

Exosomes biogenesis. In the endosomal system, endocytic vesicles fused with each other to form early endosomes (EE). There were many cargoes sequestered in EE. On one hand, the ubiquitinated proteins in EE could be sorted into intraluminal vesicles (ILVs) via ESCRT machinery. ILVs were formed through inward budding of the membrane with selected cargoes. While RNA-binding proteins heterogeneous nuclear ribonucleoprotein (hnRNP) could recognize the EXOmotifs of miRNAs and help them sorted into ILVs. On the other hand, some cargoes could be returned to the plasma membrane, called recycling endosomes. In addition, cargoes could also originate from trans-Golgi network and cytoplasm. These ILVs constituted the late endosomes /multivesicular body (LE/MVBs). The ubiquitinated targeted ILVs could be degraded within lysosome or rescue by DUBs. MVBs could also be transferred to the cell periphery via Rab27A/B. Finally, SNARE complex could help MVBs dock and fuse with plasma membrane to release ILVs into the extracellular space as exosomes