Problems in intracellular membrane traffic.

Eukaryotic cells operate an extensive and well regulated traffic of membrane-bound vesicles to: (a) transport intracellularly, and eventually discharge by exocytosis, macromolecular products; (b) take up by endocytosis molecules and particles from the environment; (c) transport macromolecules across epithelial barriers; and (d) move membranes from their site of assembly to their final locations. Vesicular transport appears to be the equivalent of a discontinuous circulatory system in which vesicles recycle between the termini of each transport pathway, so that balanced membrane distribution is maintained among cell compartments and the cell's surface. Although the general outline of the process is reasonably clear, much remains to be learned about the number and types of pathways, the types and quantities of membranes, and the rates of vesicular movement. Since each vesicular carrier finds its specific terminus (and fuses with it), vesicular traffic is strictly controlled. By analogy with the control of intracellular protein traffic, it may be assumed that vesicular traffic is regulated by the mutual recognition of protein signals and receptors affixed, in this case, with appropriate asymmetry to the surface of the interacting membranes. Since vesicular transport operates without loss of specific chemistry and function of various cellular membranes, cells can counteract effectively the randomization of membrane proteins and lipids, which becomes possible whenever two membranes establish continuity of their fluid bilayers, and when membrane is removed from one or both termini of a recycling pathway. Specific selection of termini and prevention of randomization among membrane components are major unsolved problems in vesicular transport. Their solution in terms of molecular interactions requires further work.