期刊
EMBO REPORTS
卷 20, 期 11, 页码 -出版社
WILEY
DOI: 10.15252/embr.201948336
关键词
autosomal dominant polycystic kidney disease; gain-of-function; ion channel; polycystin-1; polycystin-2
资金
- National Institutes of Health [DK102092, R01DK111611, P30DKO90868]
- PKD Foundation Research Grant [230G18a]
- Natural Sciences and Engineering Research Council of Canada [DG RGPIN 401946, 05842]
- Kidney Foundation of Canada [BRG KFOC180027]
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.
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