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J Biol Chem. 2004 Jun 11;279(24):25582-9. Epub 2004 Apr 1.

The N-terminal extracellular domain is required for polycystin-1-dependent channel activity.

Author information

1
Division of Nephrology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Abstract

Autosomal dominant polycystic kidney disease (PKD) is caused by mutation of polycystin-1 or polycystin-2. Polycystin-2 is a Ca(2+)-permeable cation channel. Polycystin-1 is an integral membrane protein of less defined function. The N-terminal extracellular region of polycystin-1 contains potential motifs for protein and carbohydrate interaction. We now report that expression of polycystin-1 alone in Chinese hamster ovary (CHO) cells and in PKD2-null cells can confer Ca(2+)-permeable non-selective cation currents. Co-expression of a loss-of-function mutant of polycystin-2 in CHO cells does not reduce polycystin-1-dependent channel activity. A polycystin-1 mutant lacking approximately 2900 amino acids of the extracellular region is targeted to the cell surface but does not produce current. Extracellular application of antibodies against the immunoglobulin-like PKD domains reduces polycystin-1-dependent current. These results support the hypothesis that polycystin-1 is a surface membrane receptor that transduces the signal via changes in ionic currents.

PMID:
15060061
DOI:
10.1074/jbc.M402829200
[Indexed for MEDLINE]
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