Once in the Golgi complex, cargo proteins must traverse this organelle, which is composed of a series of interconnected stacks of four to six flat membranous cisternae and of tubular–saccular networks located at the cis and trans poles of the stacks. The main functions of the Golgi complex are to transport and chemically process cargo proteins and lipids, activities that mostly involve glycosylation. The mechanism of cargo transfer through the Golgi complex is composite and appears to involve the process of cisternal progression–maturation for large supramolecular cargoes, as well as other mechanisms for different cargo classes.

After passing through the Golgi complex and reaching the trans-Golgi network, different cargoes are packaged in specialized membranous carriers, within which they are shipped out to their respective destinations, such as the lysosomes or the plasma membrane.20 Most proteins that are destined for the lysosomes (lysosomal enzymes) contain a mannose-6-phosphate tag and are sorted by the mannose-6-phosphate receptor into vesicles that are coated with a further protein complex, which is based on clathrin.21 Other cargoes move to the plasma membrane (or to their specific basolateral or apical domains in polarized cells) within large, apparently uncoated pleomorphic carriers that form at the trans-Golgi network. Also, in certain specialized cells, selected cargo proteins are greatly condensed into secretory granules that accumulate in the cytoplasm until their secretion is triggered by specific signals. Thus, there are several types of transport vesicles, all of which are formed by the fissioning of membrane buds from donor membranes, undergo translocation by microtubule-based motors, and dock onto and fuse with their acceptor membranes.

Once at the cell surface, most membrane proteins undergo endocytosis, a fundamental process that is involved in many functions, including control of the composition of the plasma membrane, cell signaling, and uptake of essential nutrients. There are several types of endocytic carriers, which differ in the proteins they transport, in their morphologic features and dynamics, and in their underlying molecular mechanisms.28 The best-characterized carriers are the clathrin-coated vesicles, the caveolin-coated vesicles, and the macropinosomes (pleomorphic carriers that can engulf large volumes of extracellular fluid). Phagosomes are similar to macropinosomes, and in specialized cells (e.g., macrophages) they mediate the internalization of large objects (typically bacteria), which are then digested in the lysosomes.

Most endocytic carriers then converge in the early endosomes, a vacuolar–tubular sorting station from which cargo proteins are sorted and delivered to several destinations. These destinations include the plasma membrane again; the recycling endosomes, another important sorting station from which cargo proteins can either return to the plasma membrane or move into the trans-Golgi network; and the late endosomes (the last endocytic station), from which some cargoes move to the Golgi complex and others are transferred to lysosomes for degradation. Another organelle that can fuse directly with lysosomes is the autophagosome. Autophagy is a process by which damaged cytosolic and organellar components are enveloped in specialized membranes and targeted for lysosomal degradation.