Date of Award
Autosomal dominant polycystic kidney disease is caused by mutations in polycystin-1 (also known as PKD1), a polycystic kidney disease protein, or polycystin-2 (also known as PKD2 or TRPP2), a transient receptor potential channel. 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 function assay. In this study, we dissect the role of polycystin-1 by directly recording current from a gain-of-function 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 activity. We also show that the cleavage of polycystin-1 at the N-terminal G protein-coupled receptor proteolytic 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.
Wang, Zhifei, "The ion channel function of polycystin‐1 in the polycystin‐1/polycystin‐2 complex" (2020). Theses and Dissertations. 124.