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The rat ileal apical Na+-dependent bile acid transporter (ASBT) and the liver Na+-taurocholate cotransporting polypeptide (Ntcp) are members of a new family of anion transporters. These transport proteins share limited sequence homology and almost identical predicted secondary structures but are localized to the apical surface of ileal enterocytes and the sinusoidal surface of hepatocytes, respectively. Stably transfected Madin-Darby canine kidney (MDCK) cells appropriately localized wild-type ASBT and Ntcp apically and basolaterally as assessed by functional activity and immunocytochemical localization studies. Truncated and chimeric transporters were used to determine the functional importance of the cytoplasmic tail in bile acid transport activity and membrane localization. Two cDNAs were created encoding a truncated transporter in which the 56-amino-acid COOH-terminal tail of Ntcp was removed or substituted with an eight-amino-acid epitope FLAG. For both mutants there was some loss of fidelity in basolateral sorting in that approximately 75% of each protein was delivered to the basolateral surface compared with approximately 90% of the wild-type Ntcp protein. In contrast, deletion of the cytoplasmic tail of ASBT led to complete loss of transport activity and sorting to the apical membrane. An Ntcp chimera in which the 56-amino-acid COOH-terminal tail of Ntcp was replaced with the 40-amino-acid cytoplasmic tail of ASBT was largely redirected (82.4 +/- 3.9%) to the apical domain of stably transfected MDCK cells, based on polarity of bile acid transport activity and localization by confocal immunofluorescence microscopy. These results indicate that a predominant signal for sorting of the Ntcp protein to the basolateral domain is located in a region outside of the cytoplasmic tail. These studies have further shown that a novel apical sorting signal is localized to the cytoplasmic tail of ASBT and that it is transferable and capable of redirecting a protein normally sorted to the basolateral surface to the apical domain of MDCK cells.
A Q Sun, and
M Ananthanarayanan, and
C J Soroka, and
S Thevananther, and
B L Shneider, and
F J Suchy
March 1997,
The Journal of biological chemistry,
A Q Sun, and
M Ananthanarayanan, and
C J Soroka, and
S Thevananther, and
B L Shneider, and
F J Suchy
February 2002,
Bioscience, biotechnology, and biochemistry,
A Q Sun, and
M Ananthanarayanan, and
C J Soroka, and
S Thevananther, and
B L Shneider, and
F J Suchy
September 2011,
The Journal of cell biology,
A Q Sun, and
M Ananthanarayanan, and
C J Soroka, and
S Thevananther, and
B L Shneider, and
F J Suchy
January 1991,
Current topics in microbiology and immunology,
A Q Sun, and
M Ananthanarayanan, and
C J Soroka, and
S Thevananther, and
B L Shneider, and
F J Suchy
May 2012,
Cell research,
A Q Sun, and
M Ananthanarayanan, and
C J Soroka, and
S Thevananther, and
B L Shneider, and
F J Suchy
May 1995,
Journal of lipid research,
A Q Sun, and
M Ananthanarayanan, and
C J Soroka, and
S Thevananther, and
B L Shneider, and
F J Suchy
February 1995,
Journal of pediatric gastroenterology and nutrition,
A Q Sun, and
M Ananthanarayanan, and
C J Soroka, and
S Thevananther, and
B L Shneider, and
F J Suchy
February 2017,
Yao xue xue bao = Acta pharmaceutica Sinica,
A Q Sun, and
M Ananthanarayanan, and
C J Soroka, and
S Thevananther, and
B L Shneider, and
F J Suchy
January 1998,
Advances in pharmacology (San Diego, Calif.),
A Q Sun, and
M Ananthanarayanan, and
C J Soroka, and
S Thevananther, and
B L Shneider, and
F J Suchy
December 1997,
The Journal of clinical investigation,
