PMID- 21914796
OWN - NLM
STAT- MEDLINE
DCOM- 20120116
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 47
DP  - 2011 Nov 25
TI  - Novel role for pendrin in orchestrating bicarbonate secretion in cystic fibrosis 
      transmembrane conductance regulator (CFTR)-expressing airway serous cells.
PG  - 41069-82
LID - 10.1074/jbc.M111.266734 [doi]
AB  - In most HCO(3)(-)-secreting epithelial tissues, SLC26 Cl(-)/HCO(3)(-) 
      transporters work in concert with the cystic fibrosis transmembrane conductance 
      regulator (CFTR) to regulate the magnitude and composition of the secreted fluid, 
      a process that is vital for normal tissue function. By contrast, CFTR is regarded 
      as the only exit pathway for HCO(3)(-) in the airways. Here we show that 
      Cl(-)/HCO(3)(-) anion exchange makes a major contribution to transcellular 
      HCO(3)(-) transport in airway serous cells. Real-time measurement of 
      intracellular pH from polarized cultures of human Calu-3 cells demonstrated 
      cAMP/PKA-activated Cl(-)-dependent HCO(3)(-) transport across the luminal 
      membrane via CFTR-dependent coupled Cl(-)/HCO(3)(-) anion exchange. The 
      pharmacological and functional profile of the luminal anion exchanger was 
      consistent with SLC26A4 (pendrin), which was shown to be expressed by 
      quantitative RT-PCR, Western blot, and immunofluorescence. Pendrin-mediated anion 
      exchange activity was confirmed by shRNA pendrin knockdown (KD), which markedly 
      reduced cAMP-activated Cl(-)/HCO(3)(-) exchange. To establish the relative roles 
      of CFTR and pendrin in net HCO(3)(-) secretion, transepithelial liquid secretion 
      rate and liquid pH were measured in wild type, pendrin KD, and CFTR KD cells. 
      cAMP/PKA increased the rate and pH of the secreted fluid. Inhibiting CFTR reduced 
      the rate of liquid secretion but not the pH, whereas decreasing pendrin activity 
      lowered pH with little effect on volume. These results establish that CFTR 
      predominately controls the rate of liquid secretion, whereas pendrin regulates 
      the composition of the secreted fluid and identifies a critical role for this 
      anion exchanger in transcellular HCO(3)(-) secretion in airway serous cells.
FAU - Garnett, James P
AU  - Garnett JP
AD  - Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle 
      upon Tyne NE2 4HH, United Kingdom.
FAU - Hickman, Emma
AU  - Hickman E
FAU - Burrows, Rachel
AU  - Burrows R
FAU - Hegyi, Peter
AU  - Hegyi P
FAU - Tiszlavicz, Laszlo
AU  - Tiszlavicz L
FAU - Cuthbert, Alan W
AU  - Cuthbert AW
FAU - Fong, Peying
AU  - Fong P
FAU - Gray, Michael A
AU  - Gray MA
LA  - eng
GR  - BBS/S/M/2006/13134/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110913
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Bicarbonates)
RN  - 0 (Chloride-Bicarbonate Antiporters)
RN  - 0 (Chlorides)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (SLC26A4 protein, human)
RN  - 0 (Sulfate Transporters)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Bicarbonates/*metabolism
MH  - Body Fluids/cytology/metabolism
MH  - Cell Line, Tumor
MH  - Chloride-Bicarbonate Antiporters/metabolism
MH  - Chlorides/metabolism
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Cystic Fibrosis Transmembrane Conductance 
      Regulator/deficiency/genetics/*metabolism
MH  - Epithelial Cells/metabolism
MH  - *Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Membrane Transport Proteins/deficiency/genetics/*metabolism
MH  - Rats
MH  - Respiratory System/*cytology/*metabolism
MH  - Sulfate Transporters
MH  - Thyroid Gland/cytology/metabolism
PMC - PMC3220502
EDAT- 2011/09/15 06:00
MHDA- 2012/01/17 06:00
PMCR- 2012/11/25
CRDT- 2011/09/15 06:00
PHST- 2011/09/15 06:00 [entrez]
PHST- 2011/09/15 06:00 [pubmed]
PHST- 2012/01/17 06:00 [medline]
PHST- 2012/11/25 00:00 [pmc-release]
AID - S0021-9258(20)50456-0 [pii]
AID - M111.266734 [pii]
AID - 10.1074/jbc.M111.266734 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Nov 25;286(47):41069-82. doi: 10.1074/jbc.M111.266734. Epub 
      2011 Sep 13.