title: Binding and Fusion of Extracellular Vesicles to the Plasma Membrane of Their Cell Targets.
abstract: Exosomes and ectosomes, extracellular vesicles of two types generated by all cells at multivesicular bodies and the plasma membrane, respectively, play critical roles in physiology and pathology. A key mechanism of their function, analogous for both types of vesicles, is the fusion of their membrane to the plasma membrane of specific target cells, followed by discharge to the cytoplasm of their luminal cargo containing proteins, RNAs, and DNA. Here we summarize the present knowledge about the interactions, binding and fusions of vesicles with the cell plasma membrane. The sequence initiates with dynamic interactions, during which vesicles roll over the plasma membrane, followed by the binding of specific membrane proteins to their cell receptors. Membrane binding is then converted rapidly into fusion by mechanisms analogous to those of retroviruses. Specifically, proteins of the extracellular vesicle membranes are structurally rearranged, and their hydrophobic sequences insert into the target cell plasma membrane which undergoes lipid reorganization, protein restructuring and membrane dimpling. Single fusions are not the only process of vesicle/cell interactions. Upon intracellular reassembly of their luminal cargoes, vesicles can be regenerated, released and fused horizontally to other target cells. Fusions of extracellular vesicles are relevant also for specific therapy processes, now intensely investigated.
authors: CNR Institute of Neuroscience, 20133 Milan, Italy. prada.ilaria@yahoo.it.
authors: Ilaria
authors: I
authors: Prada
authors: San Raffaele Scientific Institute, DIBIT, via Olgettina 58, 20132 Milan, Italy. meldolesi.jacopo@hsr.it.
authors: Jacopo
authors: J
authors: Meldolesi
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D055252:Cell-Derived Microparticles / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism; D006801:Humans
keywords: discharge of luminal cargoes; ectosomes; exosomes; extracellular vesicles (EVs); multivesicular bodies (MVBs); plasma membrane; receptors; retroviral-type membrane fusions; vesicle cargo