Multivesicular bodies

Multivesicular bodies are usually found in association with the Golgi apparatus and are visualized by EM as small, single membrane-bound sacs approximately 0.5 Jim in diameter. They contain several minute, spherical profiles, sometimes arranged about the periphery. They are believed to belong to the lysosome series prior to secondary lysosomes because they contain acid hydrolases and apparently are derived from primary lysosomes. 

Details of the mechanisms by which endocytosed material moves from the early to the late and lysosomal compartment are still poorly understood. However, portions of the EEs tubulovesicular structures may be actively transported along microtubules towards the perinuclear region of the cell in both neurons and non-neuronal cells. These endosomes on the move may enclose invaginated membranes and also internally bud off vesicles. For that reason, these complex structures are called multivesicular bodies (MVBs) [76]. Material returning by retrograde axonal transport to the neuronal cell body includes many MVBs [67]. The eventual fate of these structures may vary. Some MVBs may fuse with LEs or they may fuse with each... 

LDLR low density lipoprotein receptor MVB multivesicular body... 

Longva, K. E., et al., Ubiquitination and proteasomal activity is required for transport of the EGF receptor to inner membranes of multivesicular bodies. J Cell Biol, 2002, 156(5), 843-54. 

Katzmann, D. j., Babst, M., and Emr, S. D. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cdl 2001, 106, 145-55. 

Early endosomes are the main sorting station in the endocytic pathway. In their acidic interior (pH 5.9-6.0), the receptor and its ligand can be released. The receptor may be recycled to the surface by vesicles that fuse with the plasma membrane. Material that cannot escape from the early endosomes is further transported via multivesicular bodies to late endosomes and digesting lysosomes that contain a broad spectrum of peptidases and hydrolases in an acidic surrounding [for reviews on endocytosis see Refs. (10-12), for review on clathrin uptake see Refs. (9,13)]. 

Green fluorescent protein-RhoB GFP-RhoB is localized in endocytic vesicles and has been shown to highlight early endosomes, recycling endosomes, and multivesicular bodies, but is absent from lysosomes (123). Because RhoB is toxic when applied for long periods of time, the cells should be analyzed within 24 hours of transient transfection. 

Piper RC, Luzio JP. Late endosomes sorting and partitioning in multivesicular bodies. Traffic 2001 2(9) 612-621. 

Based on the knowledge of the endocytotic pathway, it is reasonable to assume that uhiquitination is reversible until the endocytosed membrane proteins such as neurotransmitter receptors are routed to the multivesicular body for lysosomal degradation. 

Figure 8 Ubiquitin and endocytosis. Receptors on the plasma membrane undergo monoubiquitination as a result of ligand (e.g., neurotransmitter). Ubiquitinated receptors bind to proteins called epsins, which in turn interact with adaptor proteins (adaptin) bound to clathrin-coated pits. Ubiquitination also functions to sort the internalized membrane protein into early endosomes, which directs them to degradation by lysosome through the multivesicular body. If ubiquitin from the endocytosed receptors is removed by an UBP, the receptor recycles back to the membrane. Proteasome inhibitors block endocytotic degradation of some proteins such as glutamate receptor subunits indicating a possible role for the proteasome.

Felder, S., K. Miller, G. Moehren, A. Ullrich, J. Schlessinger, and C. R. Hopkins. Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body. Cell. 61 623-634.1990. 

At the distal respiratory site, the alveolar epithelial cell layer is much flatter (0.1 -0.5 pm) and composed of two major cell types, squamous type I and agranular type II pneumocytes. Type I pneumocytes are non-phagocytic and highly flattened cells with broad and thin extensions. They occupy -95 % of the alveolar luminal surface, although they are less numerous than type II cells. The remaining surface is occupied by type II pneumocytes, which have blunt microvilli and contain multivesicular bodies [3, 11]. 

Shaw, J.D., Hama, H., Sohrabi, F., DeWald, D.B. and Wendland, B., 2003, PtdIns(3,5)P2 is required for delivery of endocytic cargo into the multivesicular body. Traffic 4 479—190. 

Heijnen, H.F., SchiefA.E., Fijnheer, R., Geuze, H.J. and Sixma, J.J. (1999)Activatedplatelets release two types of membrane vesicles microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 94, 3791-3799. 

Wubbolts, R., Leckie, R.S., Veenhuizen, P.T., Schwarzmann, G., Mobius, W., Hoemschemeyer, J., Slot, J.W., Geuze, H.J. and Stoorvogel, W. (2003) Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J. Biol. Chem. 278,10963-10972. 

Fuller, C.E., Felder, S., Schlessinger, J., Ullrich, A. and Hopkins, C.R. (1993) Annexin I is phosphoiylated in the multivesicular body during the processing of the epidermal growth factor receptor. J. Cell Biol. 120, 77-83. 

Katoh, K., Shibata, H., Suzuki, H., Nara, A., Ishidoh, K., Kominami, E., Yoshimori, T. and Maki, M. (2003) The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. J. Biol. Chem. 278, 39104-39113. 

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