Routes and mechanisms of extracellular vesicle uptake

By L. A. Mulcahy, R. Pink, D. Carter. Journal of Extracellular Vesicles, 2014

2,633 citations recorded by the source corpus.

Extracellular vesicles (EVs) are small vesicles released by donor cells that can be taken up by recipient cells. Despite their discovery decades ago, it has only recently become apparent that EVs play an important role in cell-to-cell communication. EVs can carry a range of nucleic acids and proteins which can have a significant impact on the phenotype of the recipient. For this phenotypic effect to occur, EVs need to fuse with target cell membranes, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest because they are deregulated in diseases such as cancer and they could be harnessed to deliver drugs to target cells. It is therefore important to understand the molecular mechanisms by which EVs are taken up into cells. This comprehensive review summarizes current knowledge of EV uptake mechanisms. Cells appear to take up EVs by a variety of endocytic pathways, including clathrin-dependent endocytosis, and clathrin-independent pathways such as caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft–mediated internalization. Indeed, it seems likely that a heterogeneous population of EVs may gain entry into a cell via more than one route. The uptake mechanism used by a given EV may depend on proteins and glycoproteins found on the surface of both the vesicle and the target cell. Further research is needed to understand the precise rules that underpin EV entry into cells.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/49b917e2d52930cef48e7c5bab5354c9bc60899a

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Citations in the corpus

Extracellular Vesicles: Unique Intercellular Delivery Vehicles. (2017, background): “Uptake of EVs into the endocytic system appears to be the most common mode of uptake and may be promoted by specific stimulation of cellular receptors by EV-bound ligands [57].”
Development of Exosome-encapsulated Paclitaxel to Overcome MDR in Cancer cells (2015, positive): “Exosomes and micelles, such as those found in Taxol, are taken up by endocytosis, but exosomes have superior uptake due to the presence of adhesion proteins, tetraspanins, integrins, immunoglobulins, proteoglycans, and lectins (42), which are not found on artificial nanoparticles.”
The Tumor Microenvironment: A Milieu Hindering and Obstructing Antitumor Immune Responses (2020, background): “For example, it was indicated that milk EVs expressing MUC1, a transmembrane glycoprotein, are taken up by DCs expressing DC-SIGN, a C-type lectin receptor, whereas EVs released by other sources that lack this protein are not internalized by the DCs (161).”
Shedding light on the cell biology of extracellular vesicles (2018, positive): “These processes are complex and depend on the origin of extracellular vesicles and on the identity and origin of the recipient cells, as well as seem to be linked to the downstream effects and processes instigated by these vesicles 134 .”
Exosome Theranostics: Biology and Translational Medicine (2018, background): “A well-summarized review described several endocytic pathways, such as macropinocytosis, clathrin-mediated endocytosis, caveolin-mediated endocytosis, lipid raft-mediated endocytosis, and phagocytosis, used by cells for exosome uptake [52].”
Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease (2019, background): “The first step of EV uptake is attachment to the target cell [reviewed by (McKelvey et al., 2015; Mulcahy et al., 2014)], possibly by tetraspanins (e.”
Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake (2016, neutral): “Once released the EVs can be internalized via endocytosis or membrane fusion, releasing their contents into ''recipient'' cells (Mulcahy et al. 2014).”
Molecular principles of metastasis: a hallmark of cancer revisited (2020, background): “In addition, exosomal internalization by target host cells activates heterogeneous endocytic pathways such as clathrin, lipid raft, and caveolinmediated uptake.(65,79,80) Exosome-mediated metastasis is not solely dependent upon tumor-released exosomes.”