Rab4 facilitates cyclic adenosine monophosphate–stimulated bile acid uptake and Na+‐taurocholate cotransporting polypeptide translocation

Cyclic adenosine monophosphate (cAMP) stimulates hepatic bile acid uptake by translocating sodium‐taurocholate (TC) cotransporting polypeptide (Ntcp) from an endosomal compartment to the plasma membrane. Rab4 is associated with early endosomes and involved in vesicular trafficking. This study was de...

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Bibliographic Details
Published in:Hepatology (Baltimore, Md.) Md.), 2008-11, Vol.48 (5), p.1665-1670
Main Authors: Schonhoff, Christopher M., Thankey, Krishna, Webster, Cynthia R.L., Wakabayashi, Yoshiyuki, Wolkoff, Allan W., Anwer, M. Sawkat
Format: Article
Language:English
Subjects:
Bile Acids and Salts - metabolism
Biological and medical sciences
Biological Transport - drug effects
Carcinoma, Hepatocellular
Cell Line, Tumor
Cell Membrane - metabolism
Cyclic AMP - pharmacology
Endosomes - metabolism
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Liver Neoplasms
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Organic Anion Transporters, Sodium-Dependent - metabolism
Protein Transport
rab4 GTP-Binding Proteins - physiology
Symporters - metabolism
Transfection
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Summary:Cyclic adenosine monophosphate (cAMP) stimulates hepatic bile acid uptake by translocating sodium‐taurocholate (TC) cotransporting polypeptide (Ntcp) from an endosomal compartment to the plasma membrane. Rab4 is associated with early endosomes and involved in vesicular trafficking. This study was designed to determine the role of Rab4 in cAMP‐induced TC uptake and Ntcp translocation. HuH‐Ntcp cells transiently transfected with empty vector, guanosine triphosphate (GTP) locked dominant active Rab4 (Rab4(GTP)), or guanosine diphosphate (GDP) locked dominant inactive Rab4 (Rab4(GDP)) were used to study the role of Rab4. Neither Rab4(GTP) nor Rab4(GDP) affected either basal TC uptake or plasma membrane Ntcp level. However, cAMP‐induced increases in TC uptake and Ntcp translocation were enhanced by Rab4(GTP) and inhibited by Rab4(GDP). In addition, cAMP increased GTP binding to endogenous Rab4 in a time‐dependent, but phosphoinositide‐3‐kinase–independent manner. Conclusion: Taken together, these results suggest that cAMP‐mediated phosphoinositide‐3‐kinase–independent activation of Rab4 facilitates Ntcp translocation in HuH‐Ntcp cells. (HEPATOLOGY 2008.)
ISSN:0270-9139
1527-3350
DOI:10.1002/hep.22495