Dynamic Localization of Hepatocellular Transporters: Role in Biliary Excretion and Impairment in Cholestasis.

Dynamic Localization of Hepatocellular Transporters: Role in Biliary Excretion and Impairment in Cholestasis. Curr Med Chem. 2017 Dec 05;: Authors: Roma MG, Barosso IR, Miszczuk GS, Crocenzi FA, Pozzi EJS Abstract Bile flow generation is driven by the vectorial transfer of osmotically active compounds from sinusoidal blood into a confined space, the bile canaliculus. Hence, localization of hepatocellular transporters relevant to bile formation is crucial for bile secretion. Hepatocellular transporters are localized either in the plasma membrane or in recycling endosomes, from where they can be relocated to the plasma membrane on demand, or endocytosed when the demand decreases. The balance between endocytic internalization/exocytic targeting to/from this recycling compartment is therefore the main determinant of the hepatic capability to generate bile, and to dispose endo- and xenobiotics. Furthermore, the exacerbated endocytic internalization is a common pathomechanisms in both experimental and human cholestasis; this results in bile secretory failure and, eventually, post-translational transporter downregulation by increased degradation. This review summarizes the proposed structural mechanisms accounting for this pathological condition (e.g., alteration of function, localization or expression of F-actin or F-actin/transporter cross-linking proteins, and switch to membrane microdomains where they can be readily endocytosed), and th...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research
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