Polycystin-2 is an essential ion channel subunit in the primary cilium of the renal collecting duct epithelium.

Abstract

Mutations in the polycystin genes, <i>PKD1</i> or <i>PKD2,</i> results in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Although a genetic basis of ADPKD is established, we lack a clear understanding of polycystin proteins' functions as ion channels. This question remains unsolved largely because polycystins localize to the primary cilium - a tiny, antenna-like organelle. Using a new ADPKD mouse model, we observe primary cilia that are abnormally long in cells associated with cysts after conditional ablation of <i>Pkd1</i> or <i>Pkd2</i>. Using primary cultures of collecting duct cells, we show that polycystin-2, but not polycystin-1, is a required subunit for the ion channel in the primary cilium. The polycystin-2 channel preferentially conducts K⁺ and Na⁺; intraciliary Ca²⁺, enhances its open probability. We introduce a novel method for measuring heterologous polycystin-2 channels in cilia, which will have utility in characterizing <i>PKD2</i> variants that cause ADPKD.