Diagrammatic representation of intracellular pathways of receptor-mediated endocytosis and trafficking: The ligand binding to specific cell surface receptor leads to a selective recruitment of ligand-receptor complexes into clathrin-coated pits. The coated pit represents a small area of the plasma membrane, which invaginates and pinch-off into vesicle in the cytosol. Coated pits and vesicles also trigger the recruitment of adapter proteins for example AP-2 and other interacting protein molecules. The caveolin pathway also internalizes the cargo complex, independent of clathrin-coated pits and the surface of caveolae is coated by caveolin. Both clathrin- and caveolin-dependent routes require dynamin protein to achieve the fission of the membrane invaginations and vesicle internalization. The ligand-receptor complexes within the cargo entering via the clathrin and caveolin pathways are usually directed to early endosomes. From the endosomes, the receptors and ligands are sorted to various subcellular locations, where the internalized molecules are either routed to degradative compartments such as the late endosomes, and/or lysosomes, or recycled to the plasma membrane via recycling endosomes. The recycled molecules can participate in several rounds of endocytosis. Alternatively, the internalized cargo molecules may be sequestered in endosomes for a longer period of time and continue to spark signaling events. Some early and late endosomes also contain membrane structures in the lumen, which are referred to as multi-vesicular bodies (MVBs). The endosome and lysosome system can also transmit and receive cargo from trans-Golgi network (TGN) involving vesicular intermediate carriers. The key proteins involved in the trafficking of molecules at different locations have been indicated such as AP-1, AP-1A, AP-1B, AP-2, AP-4, Dab-1, Esp15, GGA, PACS-1, and TIP.
