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Kidney Week

Abstract: FR-OR007

The Role of Polycystin 1 in the Polycystin-1/Polycystin-2 Channel

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic


  • Wang, Zhifei, St. John''s University, Queens, New York, United States
  • Ng, Courtney, St. John''s University, Queens, New York, United States
  • Liu, Xiong, University of Alberta, Edmonton, Alberta, Canada
  • Wang, Yan, St. John''s University, Queens, New York, United States
  • Alexander, R. Todd, University of Alberta, Edmonton, Alberta, Canada
  • Qian, Feng, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Chen, Xing-Zhen, University of Alberta, Edmonton, Alberta, Canada
  • Yu, Yong, St. John''s University, Queens, New York, United States

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either polycystin-1 (PC1), a polycystic kidney disease protein, or Polycystin-2 (PC2), a transient receptor potential channel. PC1 and PC2 form a receptor-ion channel complex with a 1 (PC1) : 3 (PC2) stoichiometry. The molecular mechanism of the function of this complex, especially the role of PC1, is largely unknown.


Full-length or fragments of PC1 was co-expressed with a gain-of-function (GOF) mutant of PC2 (PC2-GOF) in Xenopus laevis oocytes. Ion channel activity and ion permeability of the PC1/PC2 channel was measured with a two-electrode voltage clamp (TEVC) method and compared with the homomeric PC2 channel. Co-immunoprecipitation (co-IP) and surface biotinylation were used to evaluate the interaction and surface expression level.


Our results show that PC1 can form a channel with PC2-GOF with distinct properties from that of the homomeric PC2-GOF channel. Compared to the homomeric PC2-GOF channel, PC1/PC2-GOF channel is not blocked by extracellular divalent ions and has significantly higher Ca2+ permeability than PC2-GOF channel. We also found that the GPS cleavage-produced PC1 C-terminal fragment (PC1-CTF) has almost identical channel function as full-length PC1 when assembled with PC2-GOF. Further analysis shows that not only Ca2+, a lot of other monovalent ions, including some big organic ions, also permeate better through the PC1/PC2-GOF channel, compared to that of the PC2-GOF channel, indicating a relatively larger pore of the complex channel. More importantly, mutations in the pore region of either PC1 or PC2 alter the ion permeability of the PC1/PC2-GOF channel, confirming that both proteins contribute to the formation of the ion-conducting pore.


Full-length PC1 can associates with PC2-GOF to form a GOF PC1/PC2 complex channel in Xenopus oocytes. We were able to successfully record the channel current from this channel and dissect the role of PC1. In this channel, the PC1 subunit directly contributes to the channel pore formation, and the PC1-CTF is sufficient for its channel activity. The PC1/PC2-GOF channel has a distinct ion-conducting pore from that of the homomeric PC2-GOF channel and is more Ca2+ permeable.


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