Intralumenal Vesicles and Multivesicular Bodies

Multivesicular bodies or MVBs are specialized endosomes containing intraluminal vesicles or ILVs formed by inward budding of the endosomal membrane. This inward budding is coordinated by protein complexes called endosomal sorting complexes required for transport or ESCRTs.

Proteins destined for degradation or signaling proteins that are to be sequestered away from the cytosol are partitioned into these ILVs.

E3 ligases attach ubiquitin to these proteins at the plasma membrane, and the protein is internalized through receptor-mediated endocytosis. Then, the endocytic vesicle fuses with the early endosome.

Once the early endosome enters the process of maturation, four types of protein complexes, numbered ESCRT-0, I, II and III, act sequentially to recognize and sort the ubiquitin-tagged protein.

ESCRT-0 first recognizes the ubiquitinated protein on the endosomal membrane and ESCRT-I and II induce the inward budding of the membrane. ESCRT-II triggers the homo-oligomerization of ESCRT-III. The growing ESCRT-III oligomers also recruit enzymes that deubiquitinate the protein.

Then ESCRT III, along with an ATPase, Vps4, mediates the membrane fission and release of ILVs, transforming the endosome into an MVB.