Referenced in: none

Automatically associated channels: TRP , TRPP , TRPP1

Title: The polycystin complex mediates Wnt/Ca(2+) signalling.

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

Journal, date & volume: Nat. Cell Biol., 2016 May 23 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/27214281

Abstract
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.