Multivesicular bodies in neurons: Distribution, protein content, and trafficking functions

Abstract

SummaryMultivesicular bodies (MVBs) are intracellular endosomal organelles characterized by multiple internal vesicles that are enclosed within a single outer membrane. MVBs were initially regarded as purely prelysosomal structures along the degradative endosomal pathway of internalized proteins. MVBs are now known to be involved in numerous endocytic and trafficking functions, including protein sorting, recycling, transport, storage, and release. This review of neuronal MVBs summarizes their research history, morphology, distribution, accumulation of cargo and constitutive proteins, transport, and theories of functions of MVBs in neurons and glia. Due to their complex morphologies, neurons have expanded trafficking and signaling needs, beyond those of "geometrically simpler" cells, but it is not known whether neuronal MVBs perform additional transport and signaling functions. This review examines the concept of compartment-specific MVB functions in endosomal protein trafficking and signaling within synapses, axons, dendrites and cell bodies. We critically evaluate reports of the accumulation of neuronal MVBs based on evidence of stress-induced MVB formation. Furthermore, we discuss potential functions of neuronal and glial MVBs in development, in dystrophic neuritic syndromes, injury, disease, and aging. MVBs may play a role in Alzheimer's, Huntington's, and Niemann-Pick diseases, some types of frontotemporal dementia, prion and virus trafficking, as well as in adaptive responses of neurons to trauma and toxin or drug exposure. Functions of MVBs in neurons have been much neglected, and major gaps in knowledge currently exist. Developing truly MVB-specific markers would help to elucidate the roles of neuronal MVBs in intra-and intercellular signaling of normal and diseased neurons. KeywordsEndosome; Trafficking; Axonal Transport; Sorting; Release; Endocytosis; Degradation Definition of MVBs and scope of this reviewBased on their original discovery and historical tradition, MVBs are defined -as their name implies -by morphological criteria at the ultrastructural level. MVBs appear in ultrathin sections as spherical organelles characterized by a single outer ("limiting") membrane that Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Cooney et al., 2002). The small vesicles as well as the matrix, the lumenal space between the internal vesicles, are typically clear, but they can be of varying electron densities (Roizin et al., 1967). The internal vesicles can have heterogeneous sizes with a diameter of 50-100 nm, although they frequently are uniform in size, about 60-70 nm in...

Endosomal trafficking regulates receptor-mediated transcytosis of antibodies across the blood brain barrier

“…48 MVBs are now knowntobeinvolvedinnumerousendocyticandtrafficking functions; after sorting in the MVB, cargo can be routed back to the plasma membrane, moved to internal vesicles for extracellular release (as EMVs), or retained within the membrane of internal vesicles for eventual lysosomal degradation. 48,49 The current study shows the association of BBB-crossing antibody formats with known markers of MVBs; interestingly only 40% of the overall content of these biomarkers was associated with the unique, very high density population of vesicles that also contained BBB-crossing antibodies; the remaining 60% of these biomarkers was associated with late endosomes. The authors postulate that the exocytosing MVBs and late endosomes -precursors to degradative MVBs, are generated from a common precursor vesicle in which unique receptorassociated molecular chaperons determine the 'directional' fate of receptor-bound antibody.…”

Extracellular vesicles as modulators of cell-to-cell communication in the healthy and diseased brain

“…In the CNS, movements of MVBs to synapses are tightly linked to synaptic plasticity [32] and exosomes deriving from these compartments may exert alternating functions. Owing to their molecular makeup, EVs are believed to relay complex messages, superior to those of direct cell-to-cell contacts or secreted soluble factors [20].…”

The fine structure of the midgut epithelium in Xerobiotus pseudohufelandi (Iharos, 1966) (Tardigrada, Eutardigrada, Macrobiotidae)

“…Also, no Golgi complexes were detected in the cytoplasm of digestive cells, which cannot participate in MVB formation, contrary to what is known in other taxa (Martin and Spicer, 1973;Büning et al, 2008). The role of MVBs can be multiple; they may participate in enzyme accumulation (Martin and Spicer, 1973), degradation of membrane proteins (Piper and Katzmann, 2007), growth factor receptor down-regulation (Futter et al, 1996), developmental signalling (Lai et al, 2001), and finally in protein sorting, recycling, transport and release (von Bartheld and Altick, 2011). Because MVBs in X. pseudohufelandi probably are formed with the participation of coated vesicles that originate from endocytosis, we may suppose that these structures take part in the accumulation of substances (e.g.…”

“…Multivesicular bodies are round or oval organelles which possess numerous internal spherical or ellipsoidal vesicles enclosed within a single outer membrane (von Bartheld and Altick, 2011). These organelles may be formed by small vesicles that originate from Golgi complexes or from endocytosis (Martin and Spicer, 1973;Piper and Katzmann, 2007;Büning et al, 2008).…”