scholarly journals The Chloride Channel ClC-4 Co-localizes with Cystic Fibrosis Transmembrane Conductance Regulator and May Mediate Chloride Flux across the Apical Membrane of Intestinal Epithelia

2001 ◽  
Vol 277 (1) ◽  
pp. 566-574 ◽  
Author(s):  
Raha Mohammad-Panah ◽  
Cameron Ackerley ◽  
Johanna Rommens ◽  
Monideepa Choudhury ◽  
Yanchun Wang ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Channel ◽  
Apical Membrane ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Chloride Flux ◽  
Intestinal Epithelia ◽  
Cystic Fibrosis Transmembrane

Chloride channels in the apical membrane of normal and cystic fibrosis airway and intestinal epithelia

1992 ◽  
Vol 263 (1) ◽  
pp. L1-L14 ◽  
Author(s):  
M. P. Anderson ◽  
D. N. Sheppard ◽  
H. A. Berger ◽  
M. J. Welsh
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Channels ◽  
Apical Membrane ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Intestinal Epithelia ◽  
Cl Channel ◽  
Cystic Fibrosis Airway ◽  
Cl Channels ◽  
Cystic Fibrosis Transmembrane

Cl- channels located in the apical membrane of secretory epithelia play a key role in epithelial fluid and electrolyte transport. Dysfunction of one of these channels, cystic fibrosis transmembrane conductance regulator (CFTR), causes the genetic disease cystic fibrosis (CF). We review here the properties and regulation of the different types of Cl- channels that have been reported in airway and intestinal epithelia. We begin by describing the properties of the CFTR Cl- channel and then use those properties as a point of reference. We focused particularly on the evidence that localizes specific types of Cl- channel to the apical membrane. With that background, we assess the biological function of various Cl- channels in airway and intestinal epithelia.

scholarly journals Na+/H+ Exchanger Regulatory Factor 1 Overexpression-dependent Increase of Cytoskeleton Organization Is Fundamental in the Rescue of F508del Cystic Fibrosis Transmembrane Conductance Regulator in Human Airway CFBE41o- Cells

2010 ◽  
Vol 21 (1) ◽  
pp. 73-86 ◽  
Author(s):  
Maria Favia ◽  
Lorenzo Guerra ◽  
Teresa Fanelli ◽  
Rosa Angela Cardone ◽  
Stefania Monterisi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Apical Membrane ◽  
Rho Kinase ◽  
Chloride Secretion ◽  
Dominant Negative ◽  
Apical Region ◽  
Transmembrane Conductance Regulator ◽  
Regulatory Factor ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane

We have demonstrated that Na+/H+ exchanger regulatory factor 1 (NHERF1) overexpression in CFBE41o- cells induces a significant redistribution of F508del cystic fibrosis transmembrane conductance regulator (CFTR) from the cytoplasm to the apical membrane and rescues CFTR-dependent chloride secretion. Here, we observe that CFBE41o- monolayers displayed substantial disassembly of actin filaments and that overexpression of wild-type (wt) NHERF1 but not NHERF1-Δ Ezrin-Radixin-Moesin (ERM) increased F-actin assembly and organization. Furthermore, the dominant-negative band Four-point one, Ezrin, Radixin, Moesin homology (FERM) domain of ezrin reversed the wt NHERF1 overexpression-induced increase in both F-actin and CFTR-dependent chloride secretion. wt NHERF1 overexpression enhanced the interaction between NHERF1 and both CFTR and ezrin and between ezrin and actin and the overexpression of wt NHERF1, but not NHERF1-ΔERM, also increased the phosphorylation of ezrin in the apical region of the cell monolayers. Furthermore, wt NHERF1 increased RhoA activity and transfection of constitutively active RhoA in CFBE41o- cells was sufficient to redistribute phospho-ezrin to the membrane fraction and rescue both the F-actin content and the CFTR-dependent chloride efflux. Rho kinase (ROCK) inhibition, in contrast, reversed the wt NHERF1 overexpression-induced increase of membrane phospho-ezrin, F-actin content, and CFTR-dependent secretion. We conclude that NHERF1 overexpression in CFBE41o- rescues CFTR-dependent chloride secretion by forming the multiprotein complex RhoA-ROCK-ezrin-actin that, via actin cytoskeleton reorganization, tethers F508del CFTR to the cytoskeleton stabilizing it on the apical membrane.

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