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

Christopher M. Schonhoff, Krishna Thankey, Cynthia R L Webster, Yoshiyuki Wakabayashi, Allan W. Wolkoff, M. Sawkat Anwer

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1665-1670
Number of pages6
JournalHepatology
Volume48
Issue number5
DOIs
StatePublished - Nov 2008

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Taurocholic Acid
Guanosine Triphosphate
Bile Acids and Salts
Cyclic AMP
Guanosine
Diphosphates
Peptides
1-Phosphatidylinositol 4-Kinase
Cell Membrane
Endosomes
Liver

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Rab4 facilitates cyclic adenosine monophosphate-stimulated bile acid uptake and Na+-taurocholate cotransporting polypeptide translocation. / Schonhoff, Christopher M.; Thankey, Krishna; Webster, Cynthia R L; Wakabayashi, Yoshiyuki; Wolkoff, Allan W.; Anwer, M. Sawkat.

In: Hepatology, Vol. 48, No. 5, 11.2008, p. 1665-1670.

Research output: Contribution to journalArticle

Schonhoff, Christopher M. ; Thankey, Krishna ; Webster, Cynthia R L ; Wakabayashi, Yoshiyuki ; Wolkoff, Allan W. ; Anwer, M. Sawkat. / Rab4 facilitates cyclic adenosine monophosphate-stimulated bile acid uptake and Na+-taurocholate cotransporting polypeptide translocation. In: Hepatology. 2008 ; Vol. 48, No. 5. pp. 1665-1670.
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