2. Academic Validation
  3. The polycystin complex mediates Wnt/Ca(2+) signalling

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

  • Nat Cell Biol. 2016 Jul;18(7):752-764. doi: 10.1038/ncb3363.
Seokho Kim # 1,  Hongguang Nie # 1 2,  Vasyl Nesin 1,  Uyen Tran 3,  Patricia Outeda 4,  Chang-Xi Bai 1 5,  Jacob Keeling 1,  Dipak Maskey 1,  Terry Watnick 4,  Oliver Wessely 3,  Leonidas Tsiokas 1
Affiliations

Affiliations

  • 1 Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104, USA.
  • 2 Institute of Metabolic Disease Research and Drug Development, China Medical University, Liaoning Shenyang, 110001 China (H.N).
  • 3 Department of Cellular and Molecular Medicine, Cleveland Clinic, 9500 Euclid Avenue/NC10, Cleveland, OH 44195, USA.
  • 4 Division of Nephrology, Baltimore PKD Research and Clinical Core Center, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
  • 5 Department of Advanced Research on Mongolian Medicine, Research Institute for Mongolian Medicine, Inner Mongolia Medical University, Hohhot 010110, Inner Mongolia, China (CB).
  • # Contributed equally.
PMID: 27214281 DOI: 10.1038/ncb3363
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.

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