Figure 1. Pathways of apical and basolateral membrane protein targeting in an epithelial cell. Transmembrane proteins destined for apical (hatched ovals) or basolateral (plain ovals) insertion are both synthesized in the RER, transit the Golgi apparatus, and are packaged into distinct subsets of vesicles in the trans-Golgi network (TGN). These vesicles move either apically (1) or basolaterally (2) and are targeted in part due to specific sorting signals on their protein cargoes. The vesicles interact with microtubules and actin filaments as they move to the apical and basolateral poles of the cell. Exocytosis of the vesicles and insertion of the cargo into the plasma membrane is controlled by many ‘SNARE’ proteins (see text) and accessory proteins (step 3). Proteins reside at the cell surface for different periods of time (4), and subsequently many (including receptors) are recycled into the cytoplasm by clathrin-mediated endocytosis (step 5). Internalized vesicles, or endosomes (6), move through a complex series of steps, often including passage through a recycling endosome which is closely related to the TGN (7). For simplicity, recycling of basolateral proteins is not shown. Tight junctions in epithelial cells segregate apical and basolateral membrane proteins, as shown for proton pumps and the AE1 anion exchanger in Figure 2.

Figure 2. The plasma membrane of epithelial cells is segregated into apical and basolateral domains of distinct protein and lipid composition. In this section of a kidney collecting duct, double-staining by indirect immunofluorescence reveals the distinct apical versus basolateral membrane polarity of two important membrane proteins in proton-secreting intercalated cells. The vacuolar proton pumping ATPase (green) is confined to the apical membrane (and some subapical intracellular vesicles), whereas the chloride–bicarbonate exchanger AE1 (orange) is restricted to the basolateral plasma membrane of these cells. The apical and basolateral cell domains are separated at the level of the tight junctions (small arrows). Adjacent principal cells in the same epithelium are not stained with either of these antibodies, and appear as dark gaps or holes in the epithelial lining (asterisks).

Figure 3. Some proteins show a remarkable intracellular redistribution after activation of various signal transduction pathways. In this case, the aquaporin-2 (AQP2) water channel, transfected into porcine kidney epithelial LLC-PK1 cells, is located on perinuclear vesicles under nonstimulated, baseline conditions (arrows in (a)). After 10 min exposure to vasopressin, which results in an increase in intracellular cyclic AMP (cAMP), AQP2 translocation of vesicles containing AQP2 is activated and the protein is inserted by exocytosis into the plasma membrane (arrows in (b)).