The N-terminal extracellular domain is required for polycystin-1-dependent channel activity.
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.
Babich
Victor
V
Division of Nephrology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Zeng
Wei-Zhong
WZ
Yeh
Byung-Il
BI
Ibraghimov-Beskrovnaya
Oxana
O
Cai
Yiqiang
Y
Somlo
Stefan
S
Huang
Chou-Long
CL
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D011506:Proteins / Q000737:chemistry* / Q000502:physiology*; D015398:Signal Transduction; D050396:TRPP Cation Channels
D007473:Ion Channels; D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels