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Abstract: FR-PO272

Role of CFTR in Autosomal Dominant Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic


  • Cebotaru, Liudmila, Johns Hopkins University, Baltimore, Maryland, United States
  • Yanda, Murali K., Johns Hopkins University, Baltimore, Maryland, United States

Autosomal dominant kidney disease is the most common dominant genetic renal disorder in humans leading to significant health care costs. It is associated with the slow but relentless formation of multiple renal cysts driven by cAMP-dependent fluid secretion leading to considerable patient morbidity. CFTR is known to be involved in secreting fluid in ADPKD through its localization in the apical membrane. We showed that the CFTR corrector, VX-809 relocates CFTR to the basolateral membrane creating an absorptive phenotype. Thus, the plasma membrane is the expected site where CFTR functions. Here, we show that CFTR unexpectedly is located in primary cilia and plays a role in cilia length.


We used a combination of mouse models employing a conditional knockout of of pkd-/- and a mouse model bearing the R3277C mutation in PC1. We labelled kidneys with anti-CFTR, PC2 and anti-acetylated α-tubulin antibodies, the latter a common marker of the primary cilium. We also conducted immunoprecipitation studies.


We showed using confocal microscopy that CFTR can be found in the cilium of normal mice and is reduced in both pkd-/- and RC/RC mice. We found the same pattern for PC2. Interestingly colocalization of CFTR, PC2 and acetylated α-tubulin is restored by VX-809. We triple-labeled kidney sections to determine if CFTR and PC2 colocalize within the cilium. Surprisingly, CFTR and PC2 were co-localized to the cilia in normal and cystic kidneys treated with VX-809, but there was much less co-localization in the cystic kidneys. We asked whether CFTR and PC2 can move together within the cell via a close association. Our results showed that the two proteins are able to bind to one another. We next asked whether the absence of CFTR in a null mouse had any impact on cilia. To our surprise, the cilia length was about twice as long in the CFTR null mice compared to wt-CFTR containing controls. Finally, we determined, if PC2’s location in the primary cilium is altered in CFTR-null mice and found that the colocalization is decreased in CFTR-null mice.


These data suggest that CFTR does play a role in cilia both in impacting its length and the location of PC2.


  • NIDDK Support