Biliary transport systems: short-term regulation.

Bile secretion is conveyed by a large set of transporter proteins. Their activity is controlled on long- and short-term timescales. Short-term regulation of transcellular transport has to guarantee intra- and extracellular molecular homeostasis and has to meet the actual cellular metabolic needs. As transport activity depends not only on transporter expression, measurements of mRNA or protein levels will not fully predict functionality. Transporter activity is also determined by covalent modifications (e.g., phosphorylation), substrate competition, and subcellular transporter localization. The latter is a major target of short-term regulation of bile secretion and involves rapid endo- and exocytosis of transporter-bearing vesicles from and into the respective cell membrane. In liver parenchymal cells, several signaling pathways were identified that govern these processes; however, the underlying molecular mechanisms still need to be characterized. Different techniques have been employed in studies on transporter retrieval and insertion, which are discussed in this chapter.