Much is being learned about how plasma membrane composition and structure are regulated. The anatomy of vesicular trafficking has been described reasonably well, and the biochemical processes that ...achieve proper targeting of lipids and proteins are beginning to be elucidated. Information within the structures of proteins is being discovered that helps to target them to, or retain them in the endoplasmic reticulum, various portions of the Golgi, lysosomes, endosomes, or the plasma membrane. Moreover, investigators in this field are beginning to study how the cell deciphers this information. The mechanisms by which the cytoskeleton and its associated motor proteins help to move vesicles to the correct destinations are also being described, as are the coat, docking, and fusion proteins that result in formation, recognition, and fusion of vesicles with the correct target compartments. One of the most challenging problems in the field appears to be to describe the processes by which lipids and proteins are sorted to apical membranes of polarized cells, since sorting to this compartment appears to differ mechanistically from much of what is known about sorting and vesicular trafficking. In contrast to the emerging nature of knowledge concerning modulation of the function of membrane proteins by membrane lipids and the cytoskeleton, much is already known about the biochemical actions of the proteins. The action of biomembrane transport proteins depends on the formation of a barrier to the free mixing of intracellular and extracellular constituents by the membrane lipid bilayer. Moreover, transport across the membrane barrier frequently results in or requires work.
If transport proteins migrated across membranes as carriers, solutes could conceivably drive them to one face of membranes with their total chemical potential gradients. In the case of, say, an ...antiporter, the protein could then follow its gradient back to the other face of the membrane carrying a different solute against its gradient. Transport proteins do not, however, migrate across membranes to catalyze transport. Rather, they undergo conformational changes while embedded in them. In the case of transport ATPases, such conformational changes are believed to be a part of the route of transfer of the free energy in phosphoric acid anhydride bonds to that of solute gradients. In contrast to some assessments, it is found in this chapter that the kinetics of antiport and symport may be at least as complex as the kinetics of primary active transport by P- and F-/V-type ATPases. Neither a ping-pong nor a two-site simultaneous model accounts well for the antiport catalyzed by anion exchange (AE) proteins. Moreover, this antiport may exhibit apparently hyperbolic kinetics as well as positive and negative cooperativity depending upon the conditions under which transport is measured. The function of AE proteins is further complicated in vivo owing to their also serving in some cases as channels for regulation of cellular volume. These transport functions may be regulated through interdependent associations of the proteins with other membrane proteins, the cytoskeleton, and cytosolic enzymes involved in intermediary metabolism.
