Journal ArticleDOI
Differential localization of the cystic fibrosis transmembrane conductance regulator in normal and cystic fibrosis airway epithelium.
Edith Puchelle,Dominique Gaillard,Dominique Ploton,Jocelyne Hinnrasky,C Fuchey,Marie-Claude Boutterin,Jacky Jacquot,Dominique Dreyer,Andrea Pavirani,Wilfried Dalemans +9 more
TLDR
Findings are consistent with the concept that the CFTR delta Phe 508 mutation modifies the intracellular maturation and trafficking of the protein, leading to an altered subcellular distribution of the delta P he 508 mutant CFTR.Abstract:
Deletion of the amino acid residue Phe 508 of the cystic fibrosis transmembrane conductance regulator (CFTR) protein represents the most common mutation identified in cystic fibrosis (CF) patients. A monoclonal and a polyclonal antibody directed against different regions of CFTR were used to localize the CFTR protein in normal and CF airway epithelium derived from polyps of non-CF and CF subjects homozygous for the ΔPhe 508 CFTR mutation. To identify the cellular and subcellular localization of CFTR, immunofluorescent light microscopy, confocal scanning microscopy, and immunogold transmission electron microscopy were performed on cryofixed tissue. A markedly different subcellular distribution was identified between normal and CF airway epithelial cells. In normal epithelium, labeling was restricted to the surface apical compartment of the ciliated cells. In contrast, in the epithelium from homozygous ΔPhe 508 CF patients, CFTR markedly accumulated in the cytosol of all the epithelial cells. These findings...read more
Citations
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Journal ArticleDOI
The delta F508 mutation decreases the stability of cystic fibrosis transmembrane conductance regulator in the plasma membrane. Determination of functional half-lives on transfected cells.
Gergely L. Lukacs,Xiu Bao Chang,Christine E. Bear,Norbert Kartner,Abdalla J. Mohamed,John R. Riordan,Sergio Grinstein +6 more
TL;DR: The results indicate that the structural abnormality of delta F508CFTR affects not only the delivery of the protein to the plasma membrane, but also its stability therein, and suggest that overcoming the processing block at the endoplasmic reticulum may not suffice to restore normal Cl- conductance in CF.
Journal ArticleDOI
A mouse model for the delta F508 allele of cystic fibrosis.
B G Zeiher,E Eichwald,Joseph Zabner,J J Smith,A. P. Puga,P B McCray,Mario R. Capecchi,Michael J. Welsh,Kirk R. Thomas +8 more
TL;DR: A novel strategy was used to introduce the delta F508 mutation into the mouse CFTR gene and affected epithelia from homozygousDelta F508 mice lacked CFTR in the apical membrane and were Cl-impermeable, suggesting that these mice have the same cellular defect.
Journal ArticleDOI
Deformation-induced ATP release from red blood cells requires CFTR activity
TL;DR: It is concluded that deformation-induced ATP release from rabbit and human RBCs requires CFTR activity, suggesting a previously unrecognized role for CFTR in the regulation of vascular resistance.
Journal ArticleDOI
ΔF508 CFTR protein expression in tissues from patients with cystic fibrosis
TL;DR: The tissue-specific variation of ΔF508 CFTR expression from null to apparently normal amounts indicates that ΔF50 CFTR maturation can be modulated and suggests that determinants other than CFTR mislocalization should play a role in Δf508 CF respiratory and intestinal disease.
Journal ArticleDOI
Characterization of Wild-Type and ΔF508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia
Silvia M. Kreda,Marcus A. Mall,April Mengos,Lori G. Rochelle,James R. Yankaskas,John R. Riordan,Richard C. Boucher +6 more
TL;DR: The data demonstrate that WT CFTR is predominantly expressed in ciliated cells, and deltaF508 CFTR pathogenesis in native tissues, like heterologous cells, reflects loss of normal protein processing.
References
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Journal ArticleDOI
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
John R. Riordan,Johanna M. Rommens,Batsheva Kerem,Noa Alon,Richard Rozmahel,Zbyszko Grzelczak,Julian Zielenski,Si Lok,Natasa Plavsic,Jia Ling Chou,Mitchell L. Drumm,Michael C. Iannuzzi,Francis S. Collins,Lap-Chee Tsui +13 more
TL;DR: A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
Journal ArticleDOI
Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis
Seng H. Cheng,Richard J. Gregory,John Marshall,Sucharita Paul,David W. Souza,Gary A. White,Catherine R. O'Riordan,Alan E. Smith +7 more
TL;DR: It is proposed that the mutant versions of CFTR are recognized as abnormal and remain incompletely processed in the endoplasmic reticulum where they are subsequently degraded.
Journal ArticleDOI
Chloride impermeability in cystic fibrosis.
Paul M. Quinton,Paul M. Quinton +1 more
TL;DR: Results are reported which suggest that abnormally low Cl− permeability in cystic fibrosis leads to poor reabsorption of NaCl in the sweat duct, and hence to a high concentration of Na Cl in theSweat duct.
Journal ArticleDOI
Altered chloride ion channel kinetics associated with the delta F508 cystic fibrosis mutation.
Wilfried Dalemans,Pascal Barbry,Guy Champigny,Sophie Jallat,Karin Dott,Dominique Dreyer,Ronald G. Crystal,Andrea Pavirani,Jean-Pierre Lecocq,Michel Lazdunski +9 more
TL;DR: The ΔF508 mutation seems to have two major consequences, an abnormal translocation of the CFTR protein which limits membrane insertion, and an abnormal function in mediating Cl- transport.
Journal ArticleDOI
Easy identification of cDNA clones.
Ulrich Rüther,Benno Müller-Hill +1 more
TL;DR: A set of six cloning vectors, pUR 278, 288, 289, 290, 291, 292 is presented and a simple immunoenzymatic assay can be used to identify clones in such a cDNA library.