Multivesicular bodies: co-ordinated progression to maturity

Abstract

Multivesicular endosomes/bodies (MVBs) sort endocytosed proteins to different destinations. Many lysosomally directed membrane proteins are sorted onto intralumenal vesicles, whilst recycling proteins remain on the perimeter membrane from where they are removed via tubular extensions. MVBs move to the cell centre during this maturation process and, when all recycling proteins have been removed, fuse with lysosomes. Recent advances have identified endosomal-sorting complex required for transport (ESCRT)-dependent and ESCRT-independent pathways in intralumenal vesicle formation and mechanisms for sorting recycling cargo into tubules. Cytoskeletal motors, through interactions with these machineries and by regulating MVB movement, help to co-ordinate events leading to a mature, fusion-competent MVB.

Figure 1

An overview of endosomal maturation. The early endosome/immature multivesicular endosome/body (MVB) consists of vacuoles and connecting tubules that carry recycling cargo. Overlapping pools of Rab GTPases confer functional and morphological properties to each domain (assignment of Rab proteins involved in early endosome to TGN transport is based on [62]). During maturation the vacuoles enlarge and increase their complement of internal vesicles whilst the amount of tubules diminishes. The final act during maturation is Rab conversion, at which point the endosome loses the ability to exchange material and becomes competent to fuse with the lysosome. The inset shows an example of an MVB 15 min after internalisation of EGF. The gold particles are conjugated to anti-EGFR.

Figure 2

Retrieval pathways and movement. As the early endosome moves towards the cell centre, cargo (black italics) is retrieved using tubular or vesicular intermediates which themselves move using molecular motors. For simplicity, SNX1 and SNX4 are shown bound to the necks of emerging tubules, but may be enriched along the length of the tubule. The position of EHD1 relative to SNX4 during TfR recycling is not known. Clathrin coats (including buds along tubules and the flat clathrin lattice that localises to the vacuole and contains Hrs) are drawn in black. Cargo-specific adaptor proteins (grey) are also shown. Endosome motility is also controlled by the actin cytoskeleton (not shown).