Many animal cells, especially those subjected to mechanical stresses, frequently experience small ruptures in their plasma membrane. In a remarkable process thought to involve both homotypic vesicle–vesicle fusion and exocytosis, a temporary cell-surface patch is quickly fashioned from locally available internal-membrane sources, such as lysosomes. In addition to providing an emergency barrier against leaks, the patch reduces membrane tension over the wounded area, allowing the bilayer to flow back together to restore continuity and seal the puncture. This membrane repair process, the fusion and exocytosis of vesicles is triggered by the sudden increase of Ca2+, which is abundant in the extracellular space and rushes into the cell as soon as the plasma membrane is punctured. Figure 13–70 shows four examples in which regulated exocytosis leads to plasma membrane expansion.
polarized cells direct proteins from the Trans golgi network to the appropriate domain of the plasma Membrane
Most cells in tissues are polarized, with two or more molecularly and functionally distinct plasma membrane domains. This raises the general problem of how the
Figure 13–70 Four examples of regulated exocytosis leading to plasma membrane enlargement. The vesicles fusing with the plasma membrane during cytokinesis (a) and phagocytosis (b) are thought to be derived from endosomes, whereas those involved in wound repair (c) may be derived from plasma membranes. The vast amount of new plasma membrane inserted during cellularization in a fly embryo occurs by the fusion of cytoplasmic vesicles (d).
delivery of membrane from the Golgi apparatus is organized so as to maintain the differences between one cell-surface domain and another. A typical epithelial cell, for example, has an apical domain, which faces either an internal cavity or the outside world and often has specialized features such as cilia or a brush border of microvilli. It also has a basolateral domain, which covers the rest of the cell. The two domains are separated by a ring of tight junctions (see Figure 19–21), which prevent proteins and lipids (in the outer leaflet of the lipid bilayer) from diffusing between the two domains, so that the differences between the two domains are maintained.
In principle, differences between plasma membrane domains need not depend on the targeted delivery of the appropriate membrane components. Instead, membrane components could be delivered to all regions of the cell surface indiscriminately but then be selectively stabilized in some locations and selectively eliminated in others. Although this strategy of random delivery followed by selective retention or removal seems to be used in certain cases, deliveries are often specifically directed to the appropriate membrane domain. Epithelial cells lining the gut, for example, secrete digestive enzymes and mucus at their apical surface and components of the basal lamina at their basolateral surface. Such cells must have ways of directing vesicles carrying different cargoes to different plasma membrane domains. Proteins from the ER destined for different domains travel together until they reach the TGN, where they are separated and dispatched in secretory or transport vesicles to the appropriate plasma membrane domain (Figure 13–71).
The apical plasma membrane of most epithelial cells is greatly enriched in glycosphingolipids, which help protect this exposed surface from damage—for example, from the digestive enzymes and low pH in sites such as the gut or stomach, respectively. Similarly, plasma membrane proteins that are linked to the lipid bilayer by a GPI anchor (see Figure 12–52) are found predominantly in the apical plasma membrane. If recombinant DNA techniques are used to attach a GPI anchor to a protein that would normally be delivered to the basolateral surface, the protein is usually delivered to the apical surface instead. GPI-anchored proteins are thought to be directed to the apical membrane because they associate with glycosphingolipids in lipid rafts that form in the membrane of the TGN. As discussed in Chapter 10, lipid rafts form in the TGN and plasma membrane when glycosphingolipids and cholesterol molecules self-associate (see Figure 10–13).