Journal Article

The polycystin complex mediates Wnt/Ca2+ signalling

Outeda, Patricia, Tsiokas, Leonidas, Keeling, Jacob, Maskey, Dipak, Nesin, Vasyl, Nie, Hongguang, Wessely, Oliver, Kim, Seokho, Bai, Chang-Xi, Tran, Uyen, Watnick, Terry

2016

Overview

WNT ligands induce Ca 2+ signalling on target cells. PKD1 (polycystin 1) is considered an orphan, atypical G-protein-coupled receptor complexed with TRPP2 (polycystin 2 or PKD2), a Ca 2+ -permeable ion channel. Inactivating mutations in their genes cause autosomal dominant polycystic kidney disease (ADPKD), one of the most common genetic diseases. Here, we show that WNTs bind to the extracellular domain of PKD1 and induce whole-cell currents and Ca 2+ influx dependent on TRPP2. Pathogenic PKD1 or PKD2 mutations that abrogate complex formation, compromise cell surface expression of PKD1, or reduce TRPP2 channel activity suppress activation by WNTs. Pkd2 −/− fibroblasts lack WNT-induced Ca 2+ currents and are unable to polarize during directed cell migration. In Xenopus embryos, pkd1, Dishevelled 2 (dvl2) and wnt9a act within the same pathway to preserve normal tubulogenesis. These data define PKD1 as a WNT (co)receptor and implicate defective WNT/Ca 2+ signalling as one of the causes of ADPKD. Seokho et al. report that Wnt ligands bind the extracellular domain of polycystin 1 (PKD1) and induce Ca 2+ influx through the Ca 2+ -permeable ion channel TRPP2. This activity is abrogated by PKD1 mutations linked to polycystic kidney disease.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/106 / 13/89 / 13/95 / 14/1 / 45/70 / 631/136/334/1874/761 / 631/80/86 / 631/80/86/1999 / 631/80/86/2370 / 64/114 / 9/74 / 96/109 / Cancer Research / Cell adhesion & migration / Cell Biology / Developmental Biology / Kidney diseases / Life Sciences / Ligands / Medicine / Mutation / Proteins / Stem Cells