Schematic representation of ligand-mediated receptor endocytosis and trafficking pathways: Ligand-binding to cell surface receptors leads to a selective recruitment of ligand-receptor complexes (cargo) into clathrin-coated pits. The coated pit represents a small area of the plasma membrane, which invaginates and pinches off into vesicles in the cytoplasmic compartments. The coated vesicles trigger the recruitment of APs for example AP-1, AP-2, AP-3, AP-4, and AP-5 as well as other interacting protein molecules such as disabled-2 (Dab-2) and Golgi-localizing gamma adaptor homology domain binding protein (GGA). The clathrin-dependent routes require dynamin to achieve the fission of membrane invaginations and subsequent internalization of vesicle into the cell interior. The ligand-receptor complexes within the vesicles entering via clathrin pathway are usually directed to early endosomes. Within the endosomes, ligand-receptor complexes are sorted and directed to various subcellular compartments, where the internalized receptors are either routed to degradative compartments such as late endosomes, multi vascular bodies, and/or lysosomes, or recycled back to the plasma membrane via recycling endosomes. Alternatively, the internalized cargo 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 endosomes and lysosomes 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 may include: AP-1, AP-2, AP-3, AP-4, AP-5, Dab-2, and GGA.
