Ectosomes and exosomes: shedding the confusion between extracellular vesicles

•The characteristics and mechanisms of ectosomes and exosomes are defined. •Exosomes are released on the exocytosis of MVBs, whereas ectosomes are assembled and released from the plasma membrane. •Interactions of vesicles with target cells and vesicle navigation are illustrated. •The role of vesicles in cancer diagnosis and therapy is discussed. Long- and short-distance communication can take multiple forms. Among them are exosomes and ectosomes, extracellular vesicles (EVs) released from the cell to deliver signals to target cells. While most of our understanding of how these vesicles are assembled and work comes from mechanistic studies performed on exosomes, recent studies have begun to shift their focus to ectosomes. Unlike exosomes, which are released on the exocytosis of multivesicular bodies (MVBs), ectosomes are ubiquitous vesicles assembled at and released from the plasma membrane. Here we review the similarities and differences between these two classes of vesicle, suggesting that, despite their considerable differences, the functions of ectosomes may be largely analogous to those of exosomes. Both vesicles appear to be promising targets in the diagnosis and therapy of diseases, especially cancer. Long- and short-distance communication can take multiple forms. Among them are exosomes and ectosomes, extracellular vesicles (EVs) released from the cell to deliver signals to target cells. While most of our understanding of how these vesicles are assembled and work comes from mechanistic studies performed on exosomes, recent studies have begun to shift their focus to ectosomes. Unlike exosomes, which are released on the exocytosis of multivesicular bodies (MVBs), ectosomes are ubiquitous vesicles assembled at and released from the plasma membrane. Here we review the similarities and differences between these two classes of vesicle, suggesting that, despite their considerable differences, the functions of ectosomes may be largely analogous to those of exosomes. Both vesicles appear to be promising targets in the diagnosis and therapy of diseases, especially cancer. the fusion of vesicles with their membrane of origin, as described for ILVs, which can back fuse with the MVB limiting membrane. an extracellular vesicle generated by outward budding from the plasma membrane followed by pinching off and release to the extracellular space. a process by which cells internalize endosomes containing nutrients and particles and recycle part of the membrane to the cell surface. machinery including four major complexes, ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III, comprising several subunits. ESCRTs are involved in the sorting of proteins and remodeling of membranes. In addition, the ESCRTs that mediate budding are involved in the pinching off of ILVs and ectosomes. intracellular membrane-bound organelle generated by endocytosis and classified as early or late according to the time spent in the cytoplasm after their generation. fusion initiated by interaction of the external faces of the membranes. It is mediated, not by complexes of SNARE proteins, which are associated with the cytoplasmic faces of membranes, but by fusogens such as syncytin-1. the fusion of intracellular vesicles and other organelles with the plasma membrane, mediated by the establishment of specific SNARE complexes comprising one vesicle protein (vSNARE, such as VAMP7) and two plasma membrane proteins (pSNAREs). Fusion may be followed by the release of the organelle's contents to the extracellular space. an extracellular vesicle released on exocytosis of MVBs filled with ILVs. mixtures of ectosomes and exosomes released to the extracellular space. GTPase enzymes that hydrolyze GTP to GMP to release energy and participate in specific processes. a vesicle formed by budding of the limiting membrane of late endosomes that become MVBs. On exocytosis of MVBs, ILVs are released as exosomes. a membrane-bound organelle that can fuse with endosomes and other organelles. Fusion is followed by degradation of the molecules and structures released to the lumen. a process of internalization in which ruffles of plasma membrane engulf the extracellular milieu. The process occurs spontaneously and is guided neither by ligands nor by the contact of the internalizing particles. a late endosome engulfed with ILVs. the transport, release, and accumulation of EVs in the major fluids of the body. a process by which cells engulf one or more large particles (such as bacteria, apoptotic bodies, or large ectosomes). The plasma membrane wraps tightly around the particle and then internalizes it into the cytoplasmic phagocytic vacuole. small G proteins of the Ras superfamily involved in the regulation of several cellular processes, from cytoskeletal architecture to membrane budding and fusion. a family of proteins associated with the cytoplasmic face of membranes. Their complexes mediate the fusion of various organelles with the plasma membrane or other organelles.