Abstract
Intercellular communication has been known for decades to involve either direct contact between cells or to operate via circulating molecules, such as cytokines, growth factors, or lipid mediators. During the last decade, we have begun to appreciate the increasing importance of intercellular communication mediated by extracellular vesicles released by viable cells either from plasma membrane shedding (microvesicles, also named microparticles) or from an intracellular compartment (exosomes). Exosomes and microvesicles circulate in all biological fluids and can trigger biological responses at a distance. Their effects include a large variety of biological processes, such as immune surveillance, modification of tumor microenvironment, or regulation of inflammation. Extracellular vesicles can carry a large array of active molecules, including lipid mediators, such as eicosanoids, proteins, and nucleic acids, able to modify the phenotype of receiving cells. This review will highlight the role of the various lipidic pathways involved in the biogenesis and functions of microvesicles and exosomes.
Highlights
Intercellular communication has been known for decades to involve either direct contact between cells or to operate via circulating molecules, such as cytokines, growth factors, or lipid mediators
The difference between intraluminal vesicle (ILV) and exosomes might not be just a matter of name because ILVs are generated in an acidic pH environment inside the multivesicular body (MVB), and they are released into a neutral pH environment to become “exosomes”
ILV biogenesis involves interactions between the protein sorting machinery of the MVB membrane, i.e., the endosomal sorting complex required for transport (ESCRT), and various lipidic molecules
Summary
Exosomes were originally described about 30 years ago as a mechanism for clearing unneeded molecules from reticulocytes during their maturation into erythrocytes [29]. It has been shown that the bulk of material isolated as an “exosome pellet” or a “microvesicle pellet” is representative of several populations of microvesicles or exosomes [37,38,39,40] The existence of these various exosome populations suggests that there are distinct biogenesis pathways for different populations (Fig. 2). Direct degradation of microvesicles can occur in the circulation because their membrane lipids can be hydrolyzed by secreted phospholipases [18, 53], suggesting a shorter half-life than exosomes in biological fluids. Many lipid-related pathways appear to be involved in the biogenesis of exosomes (Fig. 2) Mobilization of these pathways may depend upon the type of parent cell, the nature of the initial stimulus, and the micro-environment, making possible combinations of biogenesis pathways leading to vesicles with diverse contents. Material packaging into exosomes and microvesicles appears to be highly dynamic process
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