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NHE-RF1 protein rescues [DELTA]F508-CFTR function
- Source :
- The American Journal of Physiology. May, 2007, Vol. 292 Issue 5, pL1085, 10 p.
- Publication Year :
- 2007
-
Abstract
- In cystic fibrosis (CF), the AF508-CFTR anterograde trafficking from the endoplasmic reticulum to the plasma membrane is inefficient. New strategies for increasing the delivery of [DELTA]F508-CFTR to the apical membranes are thus pathophysiologically relevant targets to study for CF treatment. Recent studies have demonstrated that PDZ-containing proteins play an essential role in determining polarized plasma membrane expression of ionic transporters. In the present study we have hypothesized that the PDZ-containing protein NHE-RF1, which binds to the carboxy terminus of CFTR, rescues AF508-CFTR expression in the apical membrane of epithelial cells. The plasmids encoding [DELTA]F508-CFTR and NHE-RF1 were intranuclearly injected in A549 or Madin-Darby canine kidney (MDCK) cells, and [DELTA]F508-CFFR channel activity was functionally assayed using SPQ fluorescent probe. Cells injected with [DELTA]F508-CFTR alone presented a low chloride channel activity, whereas its coexpression with NHE-RF1 significantly increased both the basal and forskolin-activated chloride conductances. This last effect was lost with [DELTA]F508-CFTR deleted of its 13 last amino acids or by injection of a specific NHE-RF1 antisense oligonucleotide, but not by NHE-RFI sense oligonucleotide. Immunocytochemical analysis performed in MDCK cells transiently transfected with [DELTA]F508-CFTR further revealed that NHE-RF1 specifically determined the apical plasma membrane expression of [DELTA]F508-CFTR but not that of a trafficking defective mutant potassium channel (KCNQ1). These data demonstrate that the modulation of the expression level of CFTR protein partners, like NHE-RF1, can rescue [DELTA]F508-CFTR activity. cystic fibrosis; [DELTA]F508 cystic fibrosis transmembrane conductance regulator; [Na.sup.+]/[H.sup.+] exchanger regulatory factor isoform 1; polarized expression; traffic doi:10.1152/ajplung.00445.2005
Details
- Language :
- English
- ISSN :
- 00029513
- Volume :
- 292
- Issue :
- 5
- Database :
- Gale General OneFile
- Journal :
- The American Journal of Physiology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.164253692