Shedding light on the cell biology of extracellular vesicles

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.

Main features of extracellular vesicles

a | Extracellular vesicles comprise a heterogeneous population of membrane vesicles of various origins. Their size may vary (typically between 50 nm and 500 nm, but they can be even larger, measuring 1–10 μm). Over the past two decades, extracellular vesicles have been named based on their origin (cell type), size, morphology and cargo content but can now be classified into two distinct classes: exosomes and microvesicles. b | Extracellular vesicles are formed either by budding of the plasma membrane, in which case they are referred to as microvesicles, or as intraluminal vesicles (ILVs) within the lumen of multivesicular endosomes (MVEs). MVEs fuse with the plasma membrane to release ILVs that are then called exosomes. c | Processing of extracellular vesicles for observation by conventional transmission electron microscopy (TEM) causes their shrinking, leading to an artefactual cup-shaped morphology (top panel). However, when observed in a close-to-native state by cryo-electron microscopy (cryo-EM), they appear as round structures enclosed by double-leaflet membranes (bottom panel). d | Study of extracellular vesicle composition revealed that they can carry various cargoes, including proteins, lipids and nucleic acids, and this content can vary widely between cells and conditions. The particular composition will directly affect the fate and function of extracellular vesicles, strengthening the importance of selective cargo-sorting mechanisms.