Cilium

Anatomy

Organelle

Receptor

Biology

PKD1

Endocrinology

Autosomal dominant polycystic kidney disease

Kidney

Cholangiocyte

Duct (anatomy)

Polycystic kidney disease

Ion channel

Cell biology

Genetics

eLife

Mutations in the polycystin genes, PKD1 or PKD2, 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 Pkd1 or Pkd2. 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 PKD2 variants that cause ADPKD.

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