Agonist-induced coordinated trafficking of functionally related transport proteins for water and ions in cholangiocytes.

Abstract	We previously proposed that ductal bile formation is regulated by secretin-responsive relocation of aquaporin 1 (AQP1), a water-selective channel protein, from an intracellular vesicular compartment to the apical membrane of cholangiocytes. In this study, we immunoisolated AQP1-containing vesicles from cholangiocytes prepared from rat liver; quantitative immunoblotting revealed enrichment in these vesicles of not only AQP1 but also cystic fibrosis transmembrane regulator (CFTR) and AE2, a Cl- channel and a Cl-/HCO3- exchanger, respectively. Dual labeled immunogold electron microscopy of cultured polarized mouse cholangiocytes showed significant colocalization of AQP1, CFTR, and AE2 in an intracellular vesicular compartment; exposure of cholangiocytes to dibutyryl-cAMP (100 microm) resulted in co-redistribution of all three proteins to the apical cholangiocyte plasma membrane. After administration of secretin to rats in vivo, bile flow increased, and AQP1, CFTR, and AE2 co-redistributed to the apical cholangiocyte membrane; both events were blocked by pharmacologic disassembly of microtubules. Based on these in vitro and in vivo observations utilizing independent and complementary approaches, we propose that cholangiocytes contain an organelle that sequesters functionally related proteins that can account for ion-driven water transport, that this organelle moves to the apical cholangiocyte membrane in response to secretory agonists, and that these events account for ductal bile secretion at a molecular level.
Authors	Pamela S Tietz, Raul A Marinelli, Xian-Ming Chen, Bing Huang, Jonathan Cohn, Jolanta Kole, Mark A McNiven, Seth Alper, Nicholas F LaRusso
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 278 Issue 22 Pg. 20413-9 (May 30 2003) ISSN: 0021-9258 [Print] United States
PMID	12660234 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Anion Transport Proteins Antiporters Aqp1 protein, rat Aquaporins Membrane Proteins SLC4A Proteins Water Cystic Fibrosis Transmembrane Conductance Regulator Secretin Aquaporin 1
Topics	Animals Anion Transport Proteins Antiporters Aquaporin 1 Aquaporins (metabolism) Bile Ducts, Intrahepatic (cytology, drug effects, metabolism, ultrastructure) Cystic Fibrosis Transmembrane Conductance Regulator (metabolism) Ion Transport Male Membrane Proteins (metabolism) Microscopy, Electron Protein Transport Rats Rats, Inbred F344 SLC4A Proteins Secretin (pharmacology) Water (metabolism)

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