Abstract
Emerging evidence highlights the relevance of extracellular vesicles (EVs) in modulating human diseases including but not limited to cancer, inflammation, and neurological disorders. EVs can be found in almost all types of human body fluids, suggesting that their trafficking may allow for their targeting to remote recipient cells. While molecular processes underlying EV biogenesis and secretion are increasingly elucidated, mechanisms governing EV transportation, target finding and binding, as well as uptake into recipient cells remain to be characterized. Understanding the specificity of EV transport and uptake is critical to facilitating the development of EVs as valuable diagnostics and therapeutics. In this mini review, we focus on EV uptake mechanisms and specificities, as well as their implications in human diseases.
Highlights
Biogenesis of extracellular vesicles (EVs) mainly involves (1) the outward budding followed by pinching of the plasma membrane and (2) the formation of multivesicular endosomes (MVEs) from the maturation of intraluminal vesicles (ILVs)
As opposed to MV biogenesis at the plasma membrane, exosomes originate from the endosomal compartment and involve multiple mechanisms that are responsible for processes ranging from cargo sorting to the transport and apposition of MVEs at the cell membrane for their release
Exosomes can be generated in an endosomal sorting complex required for transport (ESCRT)-independent manner involving ceramide, the syndecan/ALIX pathway and tetraspanins [18,19,20]. These mechanisms may be molecularly distinct from one another, exosome biogenesis often involves the concomitant dependence on multiple ESCRT-dependent and ESCRT-independent pathways governed by factors including cargo content, cell type, and external stimuli
Summary
With emerging functions in physiological and pathological conditions, as well as therapeutic potential, it is imperative to understand the molecular mechanisms governing EV uptake by recipient cells In this mini review, we will summarize the different ways in which EVs enter target cells and review the current knowledge on the specificity of EV uptake. Biogenesis of EVs mainly involves (1) the outward budding followed by pinching of the plasma membrane (commonly employed by MVs) and (2) the formation of multivesicular endosomes (MVEs) from the maturation of intraluminal vesicles (ILVs) (commonly employed by exosomes). As opposed to MV biogenesis at the plasma membrane, exosomes originate from the endosomal compartment and involve multiple mechanisms that are responsible for processes ranging from cargo sorting to the transport and apposition of MVEs at the cell membrane for their release.
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