Regulation of Plasma Membrane Recycling by CFTR

Bradbury, Neil A.; Jilling, Tamás; Berta, G; Sorscher, Eric J.; Bridges, Robert J.; Kirk, Kevin L.

doi:10.1126/science.1373908

Cited by 331 publications

(164 citation statements)

References 20 publications

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“…It is thus possible that both CFTR and F508del-CFTR lie mostly in the subapical region and that, upon stimulation (eg, by cAMP) CFTR, but not F508del-CFTR, undergoes exocytosis to the apical membrane, as first suggested by Bradbury et al (1992) and also by other authors (Biwersi et al, 1996;Prince et al, 1994;Takahashi et al, 1996;Tousson et al, 1996). The fact that a number of other studies reported apparently contradictory observations (Dho et al, 1993;Dunn et al, 1994;Hug et al, 1997), provides evidence that the issue of CFTR and vesicular trafficking is still an open Double labeling of CFTR, calnexin, p58, and tubulin.…”

Section: Penque Et Almentioning

confidence: 79%

Cystic Fibrosis F508del Patients Have Apically Localized CFTR in a Reduced Number of Airway Cells

Penque

Mendes

Beck

et al. 2000

Laboratory Investigation

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SUMMARY:Present state of knowledge, mostly based on heterologous expression studies, indicates that the cystic fibrosis transmembrane conductance regulator (CFTR) protein bearing the F508del mutation is misprocessed and mislocalized in the cytoplasm, unable to reach the cell surface. Recently, however, it was described that protein levels and localization are similar between F508del and wild-type CFTR in airway and intestinal tissues, but not in the sweat glands. In this study, we used immunocytochemistry with three different anti-CFTR antibodies to investigate endogenous CFTR expression and localization in nasal epithelial cells from F508del homozygous patients, F508del carriers, and non-CF individuals. On average, 300 cells were observed per individual. No significant differences were observed for cell type distributions among CF, carrier, and non-CF samples; epithelial cells made up approximately 80% to 95% of all cells present. CFTR was detected mostly in the apical region (AR) of the tall columnar epithelial (TCE) cells, ciliated or nonciliated. By confocal microscopy analysis, we show that the CFTR apical region-staining does not overlap with either anti-calnexin (endoplasmic reticulum), anti-p58 (Golgi), or anti-tubulin (cilia) stainings. The median from results with three antibodies indicate that the apical localization of CFTR happens in 22% of TCE cells from F508del homozygous patients with CF (n ϭ 12), in 42% of cells from F508del carriers (n ϭ 20), and in 56% of cells from healthy individuals (n ϭ 12). Statistical analysis indicates that differences are significant among all groups studied and for the three antibodies (p Ͻ 0.05). These results confirm the presence of CFTR in the apical region of airway cells from F508del homozygous patients; however, they also reveal that the number of cells in which this occurs is significantly lower than in F508del carriers and much lower than in healthy individuals. These findings may have an impact on the design of novel pharmacological strategies aimed at circumventing the CF defect caused by the F508del mutation. (Lab Invest 2000, 80:857-868).

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Section: Penque Et Almentioning

confidence: 79%

Cystic Fibrosis F508del Patients Have Apically Localized CFTR in a Reduced Number of Airway Cells

Penque

Mendes

Beck

et al. 2000

Laboratory Investigation

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“…Forskolin, which raised intracellular cAMP, stimulated C1-secretion by increasing the magnitude of CFTR-mediated C1 conductance in the apical membrane [32], by a PKAdependent stimulus, was capable of stimulating mucin secretion in a Ca2+-independent manner [33]. In addition, the above mentioned results of McPherson and Dormer [29] who have shown a defect in [3-adrenergic stimulation of mucin and serous protein secretion from submandibular salivary tissues from CF patients and those of Bradbury et al [34] demonstrating the correction by transfection of wild type CFTR, of the defect in cAMP-mediated endocytosis and exocytosis in CFPAC-1 cells also correlated closely with our findings.…”

Section: Discussionmentioning

confidence: 99%

Defective ATP‐dependent mucin secretion by cystic fibrosis pancreatic epithelial cells

1996

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“…[49]), very little is known about the dynamic participation of CFTR in this process. Immunolocalization assessment, reflecting the steady-state distribution of CFTR, is hampered both by the lack of highly specific anti-CFTR antibody and the low copy-number of CFTR.…”

Section: Discussionmentioning

confidence: 99%

Constitutive internalization of cystic fibrosis transmembrane conductance regulator occurs via clathrin-dependent endocytosis and is regulated by protein phosphorylation

Lukacs

Segal

Kartner

et al. 1997

Biochemical Journal

127

138

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Although the cystic fibrosis transmembrane conductance regulator (CFTR) is primarily implicated in the regulation of plasmamembrane chloride permeability, immunolocalization and functional studies indicate the presence of CFTR in the endosomal compartment. The mechanism of CFTR delivery from the cell surface to endosomes is not understood. To delineate the internalization pathway, both the rate and extent of CFTR accumulation in endosomes were monitored in stably transfected Chinese hamster ovary (CHO) cells. The role of clathrindependent endocytosis was assessed in cells exposed to hypertonic medium, potassium depletion or intracellular acid-load. These treatments inhibited clathrin-dependent endocytosis by 90 %, as verified by measurements of "#&I-transferrin uptake. Functional association of CFTR with newly formed endosomes was determined by an endosomal pH dissipation protocol [Lukacs, Chang, Kartner, Rotstein, Riordan and Grinstein (1992) J. Biol. Chem. 267, 14568-14572]. As a second approach, endocytosis of CFTR was determined after cell-surface biotinylation with the

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Regulation of Plasma Membrane Recycling by CFTR

Cited by 331 publications

References 20 publications

Cystic Fibrosis F508del Patients Have Apically Localized CFTR in a Reduced Number of Airway Cells

Cystic Fibrosis F508del Patients Have Apically Localized CFTR in a Reduced Number of Airway Cells

Defective ATP‐dependent mucin secretion by cystic fibrosis pancreatic epithelial cells

Constitutive internalization of cystic fibrosis transmembrane conductance regulator occurs via clathrin-dependent endocytosis and is regulated by protein phosphorylation

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