Date of Award
2020
Document Type
Dissertation
Degree Name
Philosophy (Ph.D)
Department
Biological Sciences
First Advisor
Yong Yu
Second Advisor
Rachel Zufferey
Third Advisor
Yan Zhu
Abstract
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.
Recommended Citation
Wang, Zhifei, "The ion channel function of polycystin‐1 in the polycystin‐1/polycystin‐2 complex" (2020). Theses and Dissertations. 124.
https://scholar.stjohns.edu/theses_dissertations/124