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Review
. 2020 Aug 8;18(1):122.
doi: 10.1186/s12964-020-00619-5.

Focus on the morphogenesis, fate and the role in tumor progression of multivesicular bodies

Xueqiang Peng  1 , Liang Yang  1 , Yingbo Ma  1 , Yan Li  1 , Hangyu Li  2
Affiliations
Review

Focus on the morphogenesis, fate and the role in tumor progression of multivesicular bodies

Xueqiang Peng et al. Cell Commun Signal. .

Abstract

Multivesicular bodies (MVBs) are endosome organelles that are gradually attracting research attention. Initially, MVBs were considered as important components of the endosomal-lysosomal degradation pathway. In recent years, with an increase in extracellular vesicle (EV) research, the biogenesis, fate, and pathological effects of MVBs have been increasingly studied. However, the mechanisms by which MVBs are sorted to the lysosome and plasma membrane remain unclear. In addition, whether the trafficking of MVBs can determine whether exosomes are released from cells, the factors are involved in cargo loading and regulating the fate of MVBs, and the roles that MVBs play in the development of disease are unknown. Consequently, this review focuses on the mechanism of MVB biogenesis, intraluminal vesicle formation, sorting of different cargoes, and regulation of their fate. We also discuss the mechanisms of emerging amphisome-dependent secretion and degradation. In addition, we highlight the contributions of MVBs to the heterogeneity of EVs, and their important roles in cancer. Thus, we attempt to unravel the various functions of MVBs in the cell and their multiple roles in tumor progression. Video Abstract.

Keywords: Amphisome; Autophagy; Cancer; Extracellular vesicles; Multivesicular body; Release; Trafficking.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
(Multivesicular body) MVB morphogenesis and possible sorting pathways: exosome release, back-fusion, and degradation in the lysosome and amphisome-dependent degradation or secretion. (1) the MVB may fuse with the plasma membrane and release the ILVs as exosomes. (2) Membrane cargo (ligand/receptor) may be recycled back to the plasma membrane or may be targeted to ILVs in the MVB. (3) MVBs can target internalized membrane cargoes (ligand/receptors) for degradation in the lysosome by fusing with lysosomes. (4) The amphisome fuses with lysosomes to form the autolysosome for degradation of cargo, or fuses with the plasma membrane, triggering extracellular component release, including dsDNA, proteins and lipids and separately, ILVs act as exosomes
Fig. 2
Fig. 2
Intracellular trafficking checkpoints involved in MVB transport and fusion. Of note, as the release of exosomes requires tightly regulated steps of transport, tethering and fusion of MVBs to the plasma membrane. Moreover, MVB acidification and PTMs (mainly ubiquitination) of membrane proteins of MVBs play important roles in the regulation of MVB fate. The core factors involved in MVB trafficking are shown in the figure, where the factor labelled with * is mainly involved in MVB-targeted lysosomal degradation
Fig. 3
Fig. 3
EVs secretion in eukaryotes. a. Multiple types of EVs originate through multivesicular endosome, plasma membrane and intracellular plasma membrane-connected compartment (IPMC) budding pathways, respectively. Importantly, exosomes are the contributors of MVBs to the total EV population(s), which are secreted during the fusion of multivesicular late endocytic compartment MVBs with the plasma membrane. Meanwhile, invadopodia (plasma membrane extensions) serve as key docking sites for exosome-containing MVBs and effectively control the quantity of exosomes secreted from cancer cells. b and c. Electron microscopy images of classical MVBs and MVB-like EV clusters, respectively. Images (b and c) were kindly provided by Fuhui Zhang (Department of Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, China)
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