Key Concepts of Section 14.4

Later Stages of the Secretory Pathway

• The trans-Golgi network 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 14-18).

• The pinching off of clathrin-coated vesicles requires dynamin, which forms a collar around the neck of the vesicle bud and hydrolyzes GTP (see Figure 14-19).

• Soluble enzymes destined for lysosomes are modified in the cis-Golgi by the addition of multiple mannose 6-phosphate (M6P) residues to their oligosaccharide chains.

• M6P receptors in the membrane of the trans-Golgi network bind proteins bearing M6P residues and direct them to late endosomes, where receptors and their ligand proteins dissociate. The receptors are then recycled to the Golgi or plasma membrane, and the lysosomal enzymes are delivered to lysosomes (see Figure 14-22).

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  Regulated secreted proteins are concentrated and stored in secretory vesicles to await a neuronal or hormonal signal for exocytosis. Protein aggregation within the trans-Golgi network may play a role in sorting secreted proteins to the regulated secretory pathway.

• Many proproteins transported through the secretory pathway undergo post-Golgi proteolytic cleavages that yield the mature, active proteins. This proteolytic maturation can occur in vesicles carrying proteins from the trans-Golgi network to the cell surface, in the late endosome, or in the lysosome.

• In polarized epithelial cells, membrane proteins destined for the apical and basolateral domains of the plasma membrane are sorted in the trans-Golgi network into different transport vesicles (see Figure 14-25). 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 basolateral membrane. Apically destined proteins are then endocytosed and moved across the cell to the apical membrane (transcytosis).