한빛사논문
- 조회2,599
Abstract
Seokho Kim1,6, Hongguang Nie1,2,6, Vasyl Nesin1, Uyen Tran3, Patricia Outeda4, Chang-Xi Bai1,5, Jacob Keeling1, DipakMaskey1, TerryWatnick4, OliverWessely3 and Leonidas Tsiokas1,7
1Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, Oklahoma 73104, USA. 2Institute of Metabolic Disease Research and Drug Development, China Medical University, Liaoning Shenyang 110001, China. 3Department of Cellular and Molecular Medicine, Cleveland Clinic, 9500 Euclid Avenue/NC10, Cleveland, Ohio 44195, USA. 4Division of Nephrology, Baltimore PKD Research and Clinical Core Center, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, Maryland 21201, USA. 5Department of Advanced Research on Mongolian Medicine, Research Institute for Mongolian Medicine, Inner Mongolia Medical University, Hohhot 010110, Inner Mongolia, China. 6These authors contributed equally to this work.
Correspondence to : Leonidas Tsiokas
Abstract
WNT ligands induce Ca2+ signalling on target cells. PKD1 (polycystin 1) is considered an orphan, atypical G-protein-coupled receptor complexed with TRPP2 (polycystin 2 or PKD2), a Ca2+-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 Ca2+ 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 Ca2+ 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/Ca2+ signalling as one of the causes of ADPKD.
논문정보
- Research article
- 2016년 05월 (BRIC 등록일 2016-05-26)
- 국외 연구진
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