Figure 1.

MVB biogenesis and exosome release. Monoubiquitination or aggregation provides the signal for trafficking of proteins and lipids to MVBs. The machinery for sorting ubiquitinated proteins involves the multi‐domain Vps27/HRS protein that acts as a bridge between monoubiquitinated transmembrane proteins and clathrin on endosomes (94). ESCRT is also a key player in MVB biogenesis. ESCRT‐I, ‐II and ‐III recognize monoubiquitinated cargoes and promote their inclusion in MVBs (95). Once completed, the ESCRT complex dissociates from the MVB membrane. Interestingly, the proteins within the ILVs are enriched for ubiquitin, indicating that not all of the ubiquitin is removed from proteins upon targeting to the MVB. Fusion of the MVB and release of the ILVs as exosomes are regulated and are known to require PLD, calcium and Rab11. PLD, phospholipase D.