Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

Abstract

Release of membrane vesicles, a process conserved in both prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy.

Fig. 1

Schematic representation of the extracellular vesicles. Major populations include exosomes, microvesicles and apoptotic bodies. To simplify the Figure, cells are not shown to release all types of vesicles

Fig. 2

Summary of some adaptive cellular responses including the newly recognized vesiculation process. Of note, apoptosis itself involves vesicle release (shedding of apoptotic microvesicles and apoptotic bodies)

Fig. 3

Size ranges of major types of membrane vesicles. While exosomes share size distribution with viruses, microvesicles overlap in size with bacteria and protein aggregates (e.g. immune complexes). Both apoptotic bodies and platelets fall into the size range of 1–5 μm

Fig. 4

Transmission electron micrograph of a platelet from normal human blood plasma releasing membrane vesicles (pMVs). Original magnification ×30,000

Fig. 5

Subcellular localization of proteins identified in exosomes (a) and MVs (b) The published proteomic studies are indicated by the name of the first author

Fig. 6

Ingenuity Pathway Analysis (IPA) of data from meta-analyses of published proteomic studies on exosomes and microvesicles. a Molecules implicated in viral entry by caveola- and clathrin-mediated endocytosis as well as by macropinocytosis. Shaded symbols represent molecules identified in exosomes. As shown, several exosomal proteins are present in the IPA knowledgebase as molecules that facilitate the entry of different viruses. b Molecules involved in integrin signaling. Shaded symbols represent published microvesicle-associated proteins as key participants of integrin signaling