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EMBO Rep. 2019 Aug 22:e48336. doi: 10.15252/embr.201948336. [Epub ahead of print]

The ion channel function of polycystin-1 in the polycystin-1/polycystin-2 complex.

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Department of Biological Sciences, St. John's University, Queens, NY, USA.
Department of Physiology, Membrane Protein Disease Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Departments of Pediatrics and Physiology, University of Alberta, Edmonton, AB, Canada.


Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2 gene, encoding the polycystic kidney disease protein polycystin-1 and the transient receptor potential channel polycystin-2 (also known as TRPP2), respectively. Polycystin-1 and polycystin-2 form a receptor-ion channel complex located in primary cilia. The function of this complex, especially the role of polycystin-1, is largely unknown due to the lack of a reliable functional assay. In this study, we dissect the role of polycystin-1 by directly recording currents mediated by a gain-of-function (GOF) polycystin-1/polycystin-2 channel. Our data show that this channel has distinct properties from that of the homomeric polycystin-2 channel. The polycystin-1 subunit directly contributes to the channel pore, and its eleven transmembrane domains are sufficient for its channel function. We also show that the cleavage of polycystin-1 at the N-terminal G protein-coupled receptor proteolysis site is not required for the activity of the GOF polycystin-1/polycystin-2 channel. These results demonstrate the ion channel function of polycystin-1 in the polycystin-1/polycystin-2 complex, enriching our understanding of this channel and its role in ADPKD.


autosomal dominant polycystic kidney disease; gain-of-function; ion channel; polycystin-1; polycystin-2

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