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Emerging roles of the actin cytoskeleton in cholangiocyte function and disease.

Actin is a ubiquitous, abundant protein whose monomers polymerize into polarized actin filaments. Within epithelial cells, filamentous actin is concentrated at the plasma membrane where a wide variety of actin-associated proteins harness the potential and structure of actin filaments to moderate functions at the plasma membrane. These functions include structural support of the plasma membrane, establishing and maintaining cell polarity, regulation of membrane protein distribution and activity and enhancing membrane vesicle trafficking. Consequently, the actin cytoskeleton contributes significantly to the cellular pathogenesis in a number of disease states. In recent years, the actin cytoskeleton has been found to contribute significantly to cholangiocyte function and disease. This includes directing cyclic adenosine monophosphate (cAMP)-mediated Cl(-) secretion, modulating vesicular trafficking at the apical membrane and initiating structural and functional alterations in ischemic bile ducts. Although much remains to be discovered, this article will highlight observations that indicate that the actin cytoskeleton plays a central role in the physiology and diseases of the intrahepatic bile duct.