FIGURE 3.

Overview of endocytosis pathways. Cells employ various mechanisms to internalize particles. Macropinocytosis involves the engulfment and import of large particles whereas phagocytosis refers to the import of smaller particles. Both processes require actin‐mediated extension of the plasma membrane to engulf the particles. Clathrin‐mediated endocytosis is a complex process requiring the formation of clathrin‐coated pits that trap extracellular particles and mediate their internalization and intracellular transport within the cell. Caveolin‐dependent endocytosis occurs via the association of particles with the caveolin‐1 protein, the major component of caveolae. Dynamin is required for both clathrin‐mediated and caveolin‐mediated endocytosis. There are other clathrin‐ and caveolin‐mediated endocytosis pathways, some requiring dynamin as well as dynamin‐independent pathways such as the CLIC/GEEC. During transcytosis, EVs endocytosed by clathrin‐ or caveolin‐mediated endocytosis, or by macropinocytosis are transported intracellularly from one luminal surface to another and released. It occurs in central nervous system endothelial cells and allows EVs to cross the blood‐brain barrier. Following uptake by the cell by any of these pathways, the internalized cargo is shuttled intracellularly (solid and dotted arrows), eventually fusing with the early endosome or the lysosome. (Dotted arrows indicate evidence of alternative destinations.). CLIC, clathrin‐independent carrier; GEEC, glycosylphosphatidylinositol‐anchored protein‐enriched endosomal compartments.