The isolated C-terminus of polycystin-1 promotes increased ATP-stimulated chloride secretion in a collecting duct cell line.
Cyst expansion in autosomal dominant polycystic kidney disease (ADPKD) requires accumulation of fluid into the cyst lumen, which is probably driven by aberrant chloride secretion by the cyst lining epithelium. Extracellular ATP is a potent stimulus for chloride secretion in many epithelial systems, and provides a plausible mechanism for secretion in ADPKD. Therefore the link between polycystin-1 and ATP-stimulated chloride secretion was investigated in the M1 cortical collecting duct cell line. M1 cells were stably transfected with a glucocorticoid-inducible cytoplasmic C-terminal polycystin-1 construct fused to a membrane expression cassette. Induction of fusion protein expression was associated with augmentation of ATP-stimulated transepithelial chloride secretion. After nystatin-induced permeabilization of the basolateral membrane, it was determined that expression of the polycystin fusion protein modulated an ATP-responsive apical chloride conductance. It is concluded that up-regulation of ATP-stimulated chloride secretion might play a significant role in cyst expansion in ADPKD.
Hooper
Kimberly M
KM
Division of Renal Medicine, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224, USA.
Unwin
Robert J
RJ
Sutters
Michael
M
D000255:Adenosine Triphosphate / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D002460:Cell Line; D018118:Chloride Channels / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D046508:Culture Techniques; D005122:Exudates and Transudates / Q000378:metabolism; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D050396:TRPP Cation Channels; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D000255:Adenosine Triphosphate; D018118:Chloride Channels; D002712:Chlorides; D011506:Proteins; D050396:TRPP Cation Channels