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

Pamela S. Tietz, Raul A. Marinelli, Xian-Ming Chen, Bing Huang, Jonathan Cohn, Jolanta Kole, Mark A. McNiven, Seth Alper, Nicholas F. LaRusso

Research output: Contribution to journalArticle

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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 μM) 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.

Original languageEnglish
Pages (from-to)20413-20419
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number22
DOIs
StatePublished - May 30 2003
Externally publishedYes

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Aquaporin 1
Carrier Proteins
Ions
Cystic Fibrosis
Water
Bile
Secretin
Membranes
Organelles
Rats
Chloride-Bicarbonate Antiporters
Aquaporins
Proteins
Relocation
Cell membranes
Immunoblotting
Microtubules
Liver
Electron microscopy
Electron Microscopy

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Agonist-induced coordinated trafficking of functionally related transport proteins for water and ions in cholangiocytes. / Tietz, Pamela S.; Marinelli, Raul A.; Chen, Xian-Ming; Huang, Bing; Cohn, Jonathan; Kole, Jolanta; McNiven, Mark A.; Alper, Seth; LaRusso, Nicholas F.

In: Journal of Biological Chemistry, Vol. 278, No. 22, 30.05.2003, p. 20413-20419.

Research output: Contribution to journalArticle

Tietz, PS, Marinelli, RA, Chen, X-M, Huang, B, Cohn, J, Kole, J, McNiven, MA, Alper, S & LaRusso, NF 2003, 'Agonist-induced coordinated trafficking of functionally related transport proteins for water and ions in cholangiocytes', Journal of Biological Chemistry, vol. 278, no. 22, pp. 20413-20419. https://doi.org/10.1074/jbc.M302108200
Tietz, Pamela S. ; Marinelli, Raul A. ; Chen, Xian-Ming ; Huang, Bing ; Cohn, Jonathan ; Kole, Jolanta ; McNiven, Mark A. ; Alper, Seth ; LaRusso, Nicholas F. / Agonist-induced coordinated trafficking of functionally related transport proteins for water and ions in cholangiocytes. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 22. pp. 20413-20419.
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