QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 15, Issue 7, 3485-3496, July 2004

This Article Full Text Full Text (PDF) MBC Videos All Versions of this Article: E03-10-0737v1 15/7/3485    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wakabayashi, Y. Articles by Arias, I. M. Search for Related Content PubMed PubMed Citation Articles by Wakabayashi, Y. Articles by Arias, I. M.

Intracellular Trafficking of Bile Salt Export Pump (ABCB11) in Polarized Hepatic Cells: Constitutive Cycling between the Canalicular Membrane and rab11-positive Endosomes

Yoshiyuki Wakabayashi ^* , Jennifer Lippincott-Schwartz , and Irwin M. Arias ^*  

^* Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111; Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

Submitted October 20, 2003; Revised April 2, 2004; Accepted April 14, 2004
Monitoring Editor: Keith Mostov

The bile salt export pump (BSEP, ABCB11) couples ATP hydrolysis with transport of bile acids into the bile canaliculus of hepatocytes. Its localization in the apical canalicular membrane is physiologically regulated by the demand to secrete biliary components. To gain insight into how such localization is regulated, we studied the intracellular trafficking of BSEP tagged with yellow fluorescent protein (YFP) in polarized WIF-B9 cells. Confocal imaging revealed that BSEP-YFP was localized at the canalicular membrane and in tubulo-vesicular structures either adjacent to the microtubule-organizing center or widely distributed in the cytoplasm. In the latter two locations, BSEP-YFP colocalized with rab11, an endosomal marker. Selective photobleaching experiments revealed that single BSEP-YFP molecules resided in canalicular membranes only transiently before exchanging with intracellular BSEP-YFP pools. Such exchange was inhibited by microtubule and actin inhibitors and was unaffected by brefeldin A, dibutyryl cyclic AMP, taurocholate, or PI 3-kinase inhibitors. Intracellular carriers enriched in BSEP-YFP elongated and dissociated as tubular elements from a globular structure adjacent to the microtubule-organizing center. They displayed oscillatory movement toward either canalicular or basolateral membranes, but only fused with the canalicular membrane. The pathway between canalicular and intracellular membranes that BSEP constitutively cycles within could serve to regulate apical pools of BSEP as well as other apical membrane transporters.

Abbreviations used: BSEP, bile salt export pump; BFA, brefeldin A.

Online version of this article contains supporting material. Online version is available at www.molbiolcell.org.

Corresponding author. E-mail address: ariasi{at}mail.nih.gov.

This article has been cited by other articles:

				D. A. J. Bow, J. L. Perry, D. S. Miller, J. B. Pritchard, and K. L. R. Brouwer Localization of P-gp (Abcb1) and Mrp2 (Abcc2) in Freshly Isolated Rat Hepatocytes Drug Metab. Dispos., January 1, 2008; 36(1): 198 - 202. [Abstract] [Full Text] [PDF]

				T. Kagawa, N. Watanabe, K. Mochizuki, A. Numari, Y. Ikeno, J. Itoh, H. Tanaka, I. M. Arias, and T. Mine Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G58 - G67. [Abstract] [Full Text] [PDF]

				P. Lam, C. L. Pearson, C. J. Soroka, S. Xu, A. Mennone, and J. L. Boyer Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1709 - C1716. [Abstract] [Full Text] [PDF]

				K. Mochizuki, T. Kagawa, A. Numari, M. J. Harris, J. Itoh, N. Watanabe, T. Mine, and I. M. Arias Two N-linked glycans are required to maintain the transport activity of the bile salt export pump (ABCB11) in MDCK II cells Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G818 - G828. [Abstract] [Full Text] [PDF]

				Y. Wakabayashi, H. Kipp, and I. M. Arias Transporters on Demand: Intracellular Reservoirs and Cycling of Bile Canalicular ABC Transporters J. Biol. Chem., September 22, 2006; 281(38): 27669 - 27673. [Full Text] [PDF]

				S. F. J. van de Graaf, Q. Chang, A. R. Mensenkamp, J. G. J. Hoenderop, and R. J. M. Bindels Direct Interaction with Rab11a Targets the Epithelial Ca2+ Channels TRPV5 and TRPV6 to the Plasma Membrane Mol. Cell. Biol., January 1, 2006; 26(1): 303 - 312. [Abstract] [Full Text] [PDF]

				Y. Wakabayashi, P. Dutt, J. Lippincott-Schwartz, and I. M. Arias Rab11a and myosin Vb are required for bile canalicular formation in WIF-B9 cells PNAS, October 18, 2005; 102(42): 15087 - 15092. [Abstract] [Full Text] [PDF]

				W. Chan, G. Calderon, A. L. Swift, J. Moseley, S. Li, H. Hosoya, I. M. Arias, and D. F. Ortiz Myosin II Regulatory Light Chain Is Required for Trafficking of Bile Salt Export Protein to the Apical Membrane in Madin-Darby Canine Kidney Cells J. Biol. Chem., June 24, 2005; 280(25): 23741 - 23747. [Abstract] [Full Text] [PDF]

				D. Wustner Mathematical Analysis of Hepatic High Density Lipoprotein Transport Based on Quantitative Imaging Data J. Biol. Chem., February 25, 2005; 280(8): 6766 - 6779. [Abstract] [Full Text] [PDF]