RT Journal Article
SR Electronic
T1 PKD2 is an essential ion channel subunit in the primary cilium of the renal collecting duct epithelium
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 215814
DO 10.1101/215814
A1 Xiaowen Liu
A1 Thuy Vien
A1 Jingjing Duan
A1 Shu-Hsien Sheu
A1 Paul G. DeCaen
A1 David E. Clapham
YR 2017
UL http://biorxiv.org/content/early/2017/11/07/215814.abstract
AB Mutations in either Pkd1 or Pkd2 result in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Although PKD2 is proposed to be an ion channel subunit, recordings of PKD2 ion channels conflict in their properties. Using a new ADPKD mouse model, we observe primary cilia are abnormally long in cells associated with cysts. Using primary cultures of collecting duct epithelial cells, we show that PKD2, but not PKD1, is a required subunit for primary cilia ion channel. The ciliary PKD2 channel conducts potassium and sodium ions, but little calcium. We also demonstrate that PKD2 is not constitutively active in the plasma membrane, but PKD2 channels are functional in primary cilia and are sensitized by high cilioplasmic [Ca2+]. We introduce a novel method for measuring PKD2 channels heterologously expressed in primary cilia of HEK-293 cells, which will have utility characterizing Pkd2 variants that cause ADPKD in their native ciliary membrane.