Novel Therapeutic Strategies for Exosome-Related Diseases

Abstract

The multivesicular body (MVB), also called late endosome, is a subset of specialized endosomal compartments rich in intraluminal vesicles (ILVs). Multiple ILVs accumulate within MVBs [1,2]. ILVs are formed by invagination of the limiting membrane of early endosomes and budding into the lumen of the organelle. ILVs sequester specific proteins, lipids and cytosolic components. Although exosome release is known to be mediated by MVB, its regulation is not fully understood. Once MVBs fuse with lysosomes, the cargo of the ILVs is degraded. On the other hand, when MVBs fuse with the plasma membrane, the contents of ILVs are secreted outside the cell via exosomes. Most synthesized proteins are modified by post-translational modifiers, which regulate the amount, localization, stability, and activity of proteins. Post-translational modifications (PTM) are involved in the regulation of cellular functions [3]. The formation of MVB is known to be regulated by the endosomal sorting complexes required for transport (ESCRT) systems [1], as well as tetraspanins and UBLs. ESCRT systems are also dependent on ubiquitination [4]. Recently, ubiquitin and UBLs were reported to be involved in the regulation of ILV and MVB. Proteins modified by ubiquitin, SUMO, or UBL3 were incorporated into MVB.