MVBs

MVBs, or multivesicular bodies, are late endosomal compartments in eukaryotic cells. They contain internal vesicles, called intraluminal vesicles (ILVs), that form by inward budding of the endosomal membrane. The ILVs accumulate within a single, larger endosome that matures into an MVB.

Formation and sorting: Cargo destined for degradation or secretion is sorted into ILVs via the ESCRT machinery (ESCRT-0, -I, -II, -III) and VPS4; ubiquitination of membrane proteins serves as a signal. ESCRT-independent routes involving lipids like ceramide and certain tetraspanins also contribute to ILV formation.

Fate: MVBs are routed to either lysosomes for degradation or the plasma membrane for exosome release. Fusion with lysosomes degrades ILVs and contents; fusion with the plasma membrane results in exosome release, enabling intercellular communication.

Physiological and clinical relevance: Exosomes carried by MVBs participate in intercellular communication, immune signaling, and modulation of the tumor microenvironment. Dysregulation of MVB trafficking or exosome release has been linked to cancer progression, neurodegenerative diseases, and certain viral processes that exploit endosomal pathways.

Detection and markers: Electron microscopy shows MVB morphology, while immunolabeling detects ILV-associated proteins such as CD63, CD9, CD81, Alix, and TSG101, which are commonly enriched in late endosomal and exosomal compartments. Understanding MVBs illuminates mechanisms of protein sorting, intercellular communication, and disease-related trafficking.