Vesicle recycling and cell-specific function in kidney epithelial cells.

Epithelial cell function depends on the precise delivery of newly synthesized and recycled membrane components to specific plasma membrane domains. The establishment and maintenance of apical and basolateral plasma membrane domains of quite distinct composition enable epithelia to undertake the vectorial transport of fluid, ions, and a variety of other molecules from one compartment to another. In many epithelia this capacity for transepithelial transport can be rapidly and reversibly modulated by prevailing physiological conditions. For example, in the collecting duct of the kidney the two epithelial cell types have both evolved efficient systems that enable such alterations in cell-specific function to occur in response to different stimuli. In both vasopressin-sensitive principal cells and the acid-secreting intercalated cells, specialized membrane patches containing water channels and proton pumps, respectively, are inserted into and removed from plasma membranes on demand and thus dramatically alter the properties of plasma membranes in these cells. Although the basic mechanism in both cells is the recycling of vesicles containing the membrane components of interest, the specific details of the process appear different in the two cell types. In the principal cell vesicle recycling is induced by a specific hormone, vasopressin, and involves clathrin-coated vesicles in the endocytotic step of the cycle. The vesicles that deliver water channels to the cell surface have not yet been identified. In the intercalated cell the transporting vesicles are highly specialized and are coated with the cytoplasmic domains of proton pumps. These vesicles do not have a clathrin coat and therefore represent a distinct class of coated vesicle. As more becomes known about transporting vesicles that are involved in different functions within the cell, it is becoming increasingly clear that it is no longer valid to separate vesicles simply into coated, i.e. clathrin-coated, and smooth vesicles. Three types of coating material have already been described on so-called coated vesicles (1, 14, 24), and it is likely that as our ability to detect the cytoplasmic domains of more proteins involved in intracellular transport increases, we will find that all vesicles are coated, but some are more coated than others. These coating molecules will include the cytoplasmic domains of proteins that are being delivered by the vesicles, as well as specific proteins that are involved in vesicle targeting, vesicle movement, and vesicle fusion or fission.