SLC26A9 stimulates CFTR expression and function in human bronchial cell lines

J Cell Physiol. 2011 Jan;226(1):212-23. doi: 10.1002/jcp.22328.

Abstract

We investigated the possible functional- and physical protein-interactions between two airway Cl(-) channels, SLC26A9 and CFTR. Bronchial CFBE41o- cell lines expressing CFTR(WT) or CFTR(ΔF508) were transduced with SLC26A9. Immunoblots identified a migrating band corresponding to SLC26A9 present in whole-cell lysates as on apical membrane of cells grown on polarized filters. CFTR levels were increased by the presence of SLC26A9 in both CFTR(WT) and CFTR(ΔF508) cell lines. In CFBE41o- cells and CFBE41o-/CFTR(WT) cells transduced with SLC26A9, currents associated to the protein expression were not detected. However, the forskolin (FK)-stimulated currents were enhanced in SLC26A9-transduced cells compared to control cells. Therefore, the presence of SLC26A9 resulted in an increase in CFTR activity (same % of CFTR((inh)-172) or GlyH-101 inhibition in both groups). In CFBE41o-/CFTR(ΔF508) cells transduced with SLC26A9 (at 27°C), a current associated to the protein expression was also lacking. FK-stimulated currents and level of CFTR((inh)-172) inhibition were not different in both groups. The presence of SLC26A9 in Xenopus oocytes expressing CFTR also enhanced the FK-stimulated currents as compared to oocytes expressing CFTR alone. This stimulation was mostly linked to CFTR. An enhancement of FK-stimulated currents was not found in oocytes co-expressing SLC26A9 and CFTR(ΔF508). In conclusion, in both protein expression systems used, SLC26A9 stimulates CFTR activity but not that of CFTR(ΔF508). Our co-immunoprecipitation studies demonstrate a physical interaction between both anion channels. We propose as an alternative hypothesis (not exclusive) to the known SLC26A9-STAS domain/CFTR interaction, that SLC26A9 favors the biogenesis and/or stabilization of CFTR, leading to stimulated currents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiporters / genetics
  • Antiporters / metabolism*
  • Bronchi / cytology*
  • Cell Line
  • Chlorides / metabolism
  • Colforsin / pharmacology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Gene Expression Regulation / physiology*
  • Humans
  • Patch-Clamp Techniques
  • Sulfate Transporters
  • Xenopus laevis

Substances

  • Antiporters
  • Chlorides
  • SLC26A9 protein, human
  • Sulfate Transporters
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Colforsin