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.
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January 28 2003
The isolated C-terminus of polycystin-1 promotes increased ATP-stimulated chloride secretion in a collecting duct cell line
Kimberly M. HOOPER;
Kimberly M. HOOPER
*Division of Renal Medicine, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224, U.S.A.
†Gerontology Research Center, Laboratory of Cellular and Molecular Biology, Baltimore, MD 21224, U.S.A.
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Robert J. UNWIN;
Robert J. UNWIN
‡Department of Nephrology & Physiology, Royal Free and University College Medical School, London, U.K.
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Michael SUTTERS
*Division of Renal Medicine, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224, U.S.A.
†Gerontology Research Center, Laboratory of Cellular and Molecular Biology, Baltimore, MD 21224, U.S.A.
Correspondence: Dr M. Sutters (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
September 10 2002
Revision Received:
October 22 2002
Accepted:
December 05 2002
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2003
2003
Clin Sci (Lond) (2003) 104 (3): 217–221.
Article history
Received:
September 10 2002
Revision Received:
October 22 2002
Accepted:
December 05 2002
Citation
Kimberly M. HOOPER, Robert J. UNWIN, Michael SUTTERS; The isolated C-terminus of polycystin-1 promotes increased ATP-stimulated chloride secretion in a collecting duct cell line. Clin Sci (Lond) 1 March 2003; 104 (3): 217–221. doi: https://doi.org/10.1042/cs1040217
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