The release of extracellular vesicles such as exosomes provides an attractive intercellular communication pathway. Exosomes are 30- to 150-nm membrane vesicles that are generated in endosomal compartment and act as intercellular mediators in both physiological and pathological context. Despite the growing interest in exosome functions, the mechanisms responsible for their biogenesis and secretion are still not completely understood. Knowledge about these mechanisms is important because they control the composition, and hence the function and secretion, of exosomes. Exosomes are produced as intraluminal vesicles in extremely dynamic endosomal organelles, which undergo various maturation processes in order to form multivesicular endosomes. Notably, the function of multivesicular endosomes is balanced between exosome secretion and lysosomal degradation. In the present review, we present and discuss each intracellular trafficking pathway that has been reported or proposed as regulating exosome biogenesis, with a particular focus on the importance of endosomal dynamics in sorting out cargo proteins to exosomes and to the secretion of multivesicular endosomes. An overall picture reveals several key mechanisms, which mainly act at the crossroads of endosomal pathways as regulatory checkpoints of exosome biogenesis.
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Cover Image
Cover Image
Recent advances in extracellular vesicle (EV) research have given rise to a new paradigm in cellular communication. EVs are small membrane vesicles released by cells that can be visualized by cryo-electron microscopy in a close to native state. The cover image shows vesicles released from skin cells called melanocytes and reveals their elegant but simple structure (for details see van Niel et al. (2015) Cell Rep. 13, 43-51). In this issue of Essays in Biochemistry, the role of EVs (exosomes and microvesicles) in extracellular communication has been approached from multiple perspectives: intracellular sorting and vesicle biogenesis, complex physiological systems including cardiovascular biology, metabolism and development, as well as pathophysiologic deviations including cancer and infection. Model organisms, key research tools in cell developmental biology research, have been highlighted as well. EVs, because of their role in cell-to-cell communication and their broad distribution across phyla and even kingdoms, represent a new frontier in biological and medical science. Image credit: Guillaume van Niel and Daniel Levy (Institut Curie).
To be or not to be... secreted as exosomes, a balance finely tuned by the mechanisms of biogenesis
Philip Stahl, Graça Raposo, Roberta Palmulli, Guillaume van Niel; To be or not to be... secreted as exosomes, a balance finely tuned by the mechanisms of biogenesis. Essays Biochem 15 May 2018; 62 (2): 177–191. doi: https://doi.org/10.1042/EBC20170076
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