![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 16, Issue 5, 2154-2167, May 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
F508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia
* Cystic Fibrosis/Pulmonary Research and Treatment Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248;
Mayo Foundation, S. C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, AZ 85259
Submitted November 17, 2004;
Revised January 31, 2005;
Accepted February 9, 2005
Monitoring Editor: Keith Mostov
Previous studies in native tissues have produced conflicting data on the localization and metabolic fate of WT and 
F508 cystic fibrosis transmembrane regulator (CFTR) in the lung. Combining immunocytochemical and biochemical studies utilizing new high-affinity CFTR mAbs with ion transport assays, we examined both 1) the cell type and region specific expression of CFTR in normal airways and 2) the metabolic fate of F508 CFTR and associated ERM proteins in the cystic fibrosis lung. Studies of lungs from a large number of normal subjects revealed that WT CFTR protein localized to the apical membrane of ciliated cells within the superficial epithelium and gland ducts. In contrast, other cell types in the superficial, gland acinar, and alveolar epithelia expressed little WT CFTR protein. No F508 CFTR mature protein or function could be detected in airway specimens freshly excised from a large number of F508 homozygous subjects, despite an intact ERM complex. In sum, our data demonstrate that WT CFTR is predominantly expressed in ciliated cells, and F508 CFTR pathogenesis in native tissues, like heterologous cells, reflects loss of normal protein processing.
Abbreviations used: ASL, airway surface liquid; AQP5, aquaporin 5; CF, cystic fibrosis; CFTR, cystic fibrosis transmembrane conductance regulator; F508; F, phenylalanine508 deletion; DIC, differential interference contrast; ERM, ezrin-radixin-moesin; EBP50, ERM binding protein50; Isc, short circuit current; IBMX, 3-isobutyl-1-methylxanthine; ISH, in situ hybridization; LCM, laser confocal microscopy; NL, normal; PM, plasma membrane; Rte, transepithelial resistance; Vte, transepithelial voltage.
These authors contributed equally to this work.
Address correspondence to: Silvia M. Kreda (silkre{at}med.unc.edu).
This article has been cited by other articles:
|
|
 |
|
  X.-b. Chang, A. Mengos, Y.-x. Hou, L. Cui, T. J. Jensen, A. Aleksandrov, J. R. Riordan, and M. Gentzsch Role of N-linked oligosaccharides in the biosynthetic processing of the cystic fibrosis membrane conductance regulator J. Cell Sci., September 1, 2008; 121(17): 2814 - 2823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Rollins, M. Burn, R. D. Coakley, L. A. Chambers, A. J. Hirsh, M. T. Clunes, M. I. Lethem, S. H. Donaldson, and R. Tarran A2B Adenosine Receptors Regulate the Mucus Clearance Component of the Lung's Innate Defense System Am. J. Respir. Cell Mol. Biol., August 1, 2008; 39(2): 190 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Norez, M. Pasetto, M. C. Dechecchi, E. Barison, C. Anselmi, A. Tamanini, F. Quiri, L. Cattel, P. Rizzotti, F. Dosio, et al. Chemical conjugation of {Delta}F508-CFTR corrector deoxyspergualin to transporter human serum albumin enhances its ability to rescue Cl- channel functions Am J Physiol Lung Cell Mol Physiol, August 1, 2008; 295(2): L336 - L347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Kreda, S. F. Okada, C. A. van Heusden, W. O'Neal, S. Gabriel, L. Abdullah, C. W. Davis, R. C. Boucher, and E. R. Lazarowski Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells J. Physiol., October 1, 2007; 584(1): 245 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Ostedgaard, C. S. Rogers, Q. Dong, C. O. Randak, D. W. Vermeer, T. Rokhlina, P. H. Karp, and M. J. Welsh Processing and function of CFTR-{Delta}F508 are species-dependent PNAS, September 25, 2007; 104(39): 15370 - 15375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Ianowski, J. Y. Choi, J. J. Wine, and J. W. Hanrahan Mucus secretion by single tracheal submucosal glands from normal and cystic fibrosis transmembrane conductance regulator knockout mice J. Physiol., April 1, 2007; 580(1): 301 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Wu, M. E. Krouse, and J. J. Wine Acinar origin of CFTR-dependent airway submucosal gland fluid secretion Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L304 - L311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. F. Okada, R. A. Nicholas, S. M. Kreda, E. R. Lazarowski, and R. C. Boucher Physiological Regulation of ATP Release at the Apical Surface of Human Airway Epithelia J. Biol. Chem., August 11, 2006; 281(32): 22992 - 23002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Machen Innate immune response in CF airway epithelia: hyperinflammatory? Am J Physiol Cell Physiol, August 1, 2006; 291(2): C218 - C230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Davidson, G. McLachlan, A. Wilson, A. C. Boyd, A. Doherty, G. MacGregor, L. Davies, H. A. Painter, R. Coles, S. C. Hyde, et al. Human-Specific Cystic Fibrosis Transmembrane Conductance Regulator Antibodies Detect In Vivo Gene Transfer to Ovine Airways Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 72 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Randell, R. C. Boucher, and for the University of North Carolina Virtual Lung Effective Mucus Clearance Is Essential for Respiratory Health Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 20 - 28. [Full Text] [PDF]
|
|
|
|
|
|
N. S. Joo, T. Irokawa, R. C. Robbins, and J. J. Wine Hyposecretion, Not Hyperabsorption, Is the Basic Defect of Cystic Fibrosis Airway Glands J. Biol. Chem., March 17, 2006; 281(11): 7392 - 7398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Wine Acid in the airways. Focus on "Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis" Am J Physiol Cell Physiol, March 1, 2006; 290(3): C669 - C671. [Full Text] [PDF]
|
|
|
|
|
|
Y. Song, D. Salinas, D. W. Nielson, and A. S. Verkman Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis Am J Physiol Cell Physiol, March 1, 2006; 290(3): C741 - C749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Tabary, H. Corvol, E. Boncoeur, K. Chadelat, C. Fitting, J. M. Cavaillon, A. Clement, and J. Jacquot Adherence of airway neutrophils and inflammatory response are increased in CF airway epithelial cell-neutrophil interactions Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L588 - L596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. T. Ballard, L. Trout, J. Garrison, and S. K. Inglis Ionic mechanism of forskolin-induced liquid secretion by porcine bronchi Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L97 - L104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R. Thelin, M. Kesimer, R. Tarran, S. M. Kreda, B. R. Grubb, J. K. Sheehan, M. J. Stutts, and S. L. Milgram The Cystic Fibrosis Transmembrane Conductance Regulator Is Regulated by a Direct Interaction with the Protein Phosphatase 2A J. Biol. Chem., December 16, 2005; 280(50): 41512 - 41520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Bebok, J. F. Collawn, J. Wakefield, W. Parker, Y. Li, K. Varga, E. J. Sorscher, and J. P. Clancy Failure of cAMP agonists to activate rescued {Delta}F508 CFTR in CFBE41o- airway epithelial monolayers J. Physiol., December 1, 2005; 569(2): 601 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bachhuber, J. Konig, T. Voelcker, B. Murle, R. Schreiber, and K. Kunzelmann Cl- Interference with the Epithelial Na+ Channel ENaC J. Biol. Chem., September 9, 2005; 280(36): 31587 - 31594. [Abstract] [Full Text] [PDF]
|
|
