A regulatory role of polycystin-1 on cystic fibrosis transmembrane conductance regulator plasma membrane expression

Cell Physiol Biochem. 2006;18(1-3):9-20. doi: 10.1159/000095133. Epub 2006 Aug 14.


Autosomal dominant polycystic kidney disease (ADPKD) is caused by genetic mutations in either PKD1 or PKD2, the genes that encode polycystin-1 (PC-1) and polycystin-2 (PC-2), respectively. ADPKD is characterized by the formation of multiple, progressive, fluid-filled renal cysts. To elucidate the mechanism of fluid secretion by ADPKD cysts, we examined the effect of PC-1 on the plasma membrane expression of cystic fibrosis transmembrane conductance regulator (CFTR), a key Cl(-) secretory protein. Five stably transfected MDCK lines were used in this study: two transfected with empty vector (control cells) and three expressing human PC-1 (PC-1 cells). The cAMP-induced endogenous short circuit currents (I(sc)) were smaller in PC-1 cells than in control cells. Compared to control cells, PC-1 cells transiently expressing pEGFP-CFTR showed significant reduction of whole cell cAMP-activated Cl(-) currents. Cell surface biotinylation experiments also indicated a reduction in surface expression of CFTR in PC-1 cells compared to control. Furthermore, studies using CHO cells transiently expressing PC-1 and CFTR suggest the importance of the PC-1 COOH-terminus in the observed reduction of CFTR plasma membrane expression. No differences in either endogeneous K(+) currents or P2Y receptor responses were observed between PC-1 and control cells, indicating the specificity of PC-1's action. These results indicate that PC-1 selectively maintains low cell surface expression of CFTR. Moreover, these findings suggest that the malfunction of PC-1 enhances plasma membrane expression of CFTR, thus causing abnormal Cl(-)secretion into the cyst lumen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Membrane / physiology*
  • Chloride Channels / genetics
  • Chloride Channels / physiology
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / pharmacology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology*
  • Gene Expression
  • Green Fluorescent Proteins / genetics
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • Membrane Potentials / drug effects
  • Recombinant Fusion Proteins / genetics
  • TRPP Cation Channels / metabolism*
  • Transfection


  • Chloride Channels
  • Recombinant Fusion Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Green Fluorescent Proteins
  • Hepatocyte Growth Factor
  • Cyclic AMP