Figure 1.

Schematic figure of the multivesicular body (MVB) membrane protein sorting mechanism. Cargo membrane proteins are ubiquitinated by E3 ubiquitin ligases and internalized through endocytosis. After sorting into early endosomes, the cargo membrane proteins interact with ESCRT-complexes I and II in the MVB limiting membrane and are inserted into MVB inner vesicles via actions of ESCRT-III and Vps4. The latter is coordinated by LIP5 which directly binds ESCRT-III and Vps4 and co-localizes with the membrane protein cargo inside the MVB inner vesicles. Finally, the MVBs may fuse with lysosomes, resulting in cargo protein degradation or they may fuse with the plasma membrane upon which the MVB inner vesicles are released extracellularly as exosomes. Black arrows indicate translocation events, attachment of ubiquitin and assembly/disassembly of the ESCRT-III complex.