title: The polycystin complex mediates Wnt/Ca(2+) signalling.
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.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104, USA.
authors.forename: Seokho
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104, USA.|Institute of Metabolic Disease Research and Drug Development, China Medical University, Liaoning Shenyang, 110001 China (H.N).
authors.forename: Hongguang
authors.initials: H
authors.lastname: Nie
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104, USA.
authors.forename: Vasyl
authors.initials: V
authors.lastname: Nesin
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic, 9500 Euclid Avenue/NC10, Cleveland, OH 44195, USA.
authors.forename: Uyen
authors.initials: U
authors.lastname: Tran
authors.affiliation: Division of Nephrology, Baltimore PKD Research and Clinical Core Center, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Outeda
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104, USA.|Department of Advanced Research on Mongolian Medicine, Research Institute for Mongolian Medicine, Inner Mongolia Medical University, Hohhot 010110, Inner Mongolia, China (CB).
authors.forename: Chang-Xi
authors.initials: CX
authors.lastname: Bai
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Keeling
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104, USA.
authors.forename: Dipak
authors.initials: D
authors.lastname: Maskey
authors.affiliation: Division of Nephrology, Baltimore PKD Research and Clinical Core Center, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Watnick
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic, 9500 Euclid Avenue/NC10, Cleveland, OH 44195, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Wessely
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104, USA.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Tsiokas
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D000072261:Dishevelled Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D011485:Protein Binding; D050396:TRPP Cation Channels / Q000378:metabolism; D060449:Wnt Signaling Pathway; D014981:Xenopus
chemical_list: D002118:Calcium; D000072261:Dishevelled Proteins; D050396:TRPP Cation Channels