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

Masahiro Ikeda, Peying Fong, Jie Cheng, Alessandra Boletta, Feng Qian, Xue Mei Zhang, Hui Cai, Gregory G. Germino, William B. Guggino

Research output: Contribution to journalArticlepeer-review


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 (Isc) 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.

Original languageEnglish
Pages (from-to)9-20
Number of pages12
JournalCellular Physiology and Biochemistry
Issue number1-3
Publication statusPublished - 2006


  • CFTR
  • Cyst
  • Polycystic kidney disease
  • Polycystin-1
  • Secretion

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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