Shedding light on the cell biology of extracellular vesicles

The secretion of extracellular vesicles was initially described as a means of selective elimination of proteins, lipids and RNA from cells. Now, extracellular vesicles are also considered a new mode of intercellular communication.In any given setting, the population of extracellular vesicles comprises diverse subpopulations that can differ in size, morphology, composition or biogenic mechanisms. Complementary methods of analysis are required to distinguish between these subpopulations.Several machineries, prominently including components of the endocytic sorting machineries, act concomitantly for the generation of extracellular vesicles. As a result, extracellular vesicles can vary widely in terms of their composition and may carry specific sets of proteins, lipids or RNA species that then determine their fate and functions.Generation of extracellular vesicles requires the fine-tuning of various intracellular trafficking processes, which define the composition of nascent vesicles and affect their generation and, in the case of exosomes, their secretion from an intracellular compartment.Interactions of extracellular vesicles with recipient cells can have various effects on the target cell, from stimulating signalling pathways to providing trophic support, depending on the mode of interaction and on the intracellular fate of the vesicles in case of their uptake.Studies of the cell biology of extracellular vesicles is not only essential for addressing cell biological questions but also critical to open new avenues for their clinical use as biomarkers, as cargo vehicles for the targeted delivery of compounds or as specific modulators of cell behaviours.