Protein Sorting and Processing in Later Stages of the Secretory Pathway
■ The trans-Golgi network (TGN) is a major branch point in the secretory pathway where soluble secreted proteins, lysosomal proteins, and in some cells membrane proteins destined for the basolateral or apical plasma membrane are segregated into different transport vesicles.
■ Many vesicles that bud from the trans-Golgi network as well as endocytic vesicles bear a coat composed of AP (adapter protein) complexes and clathrin (see Figure 17-19).
■ Pinching off of clathrin-coated vesicles requires dy-namin, which forms a collar around the neck of the vesicle bud and hydrolyzes GTP (see Figure 17-20).
■ Soluble enzymes destined for lysosomes are modified in the cis-Golgi yielding multiple mannose 6-phosphate (M6P) residues on their oligosaccharide chains.
■ M6P receptors in the membrane of the trans-Golgi network bind proteins bearing M6P residues and direct their transfer to late endosomes, where receptors and their lig-and proteins dissociate. The receptors then are recycled to the Golgi or plasma membrane, and the lysosomal enzymes are delivered to lysosomes (see Figure 17-23).
■ Regulated secreted proteins are concentrated and stored in secretory vesicles to await a neural or hormonal signal for exocytosis. Protein aggregation within the trans-Golgi network may play a role in sorting secreted proteins to the regulated pathway.
■ Many proteins transported through the secretory pathway undergo post-Golgi proteolytic cleavages that yield the mature, active proteins. Generally, proteolytic maturation can occur in vesicles carrying proteins from the trans-Golgi network to the cell surface, in the late endosome, or in the lysosomal.
■ In polarized epithelial cells, membrane proteins destined for the apical or basolateral domains of the plasma membrane are sorted in the trans-Golgi network into different transport vesicles (see Figure 17-26). The GPI anchor is the only apical-basolateral sorting signal identified so far.
■ In hepatocytes and some other polarized cells, all plasma-membrane proteins are directed first to the baso-lateral membrane. Apically destined proteins then are en-docytosed and moved across the cell to the apical membrane (transcytosis).
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