Cellular and Molecular Life Sciences CMLS

, Volume 59, Issue 4, pp 682–693

Molecular basis of autosomal-dominant polycystic kidney disease

  • A. R. Gallagher
  • S. Hidaka
  • N. Gretz
  • R. Witzgall

Abstract.

Autosomal-dominant polycystic kidney disease (ADPKD) is one of the most common monogenetic diseases in humans. The discovery that mutations in the PKD1 and PKD2 genes are responsible for ADPKD has sparked extensive research efforts into the physiological and pathogenetic role of polycystin-1 and polycystin-2, the proteins encoded by these two genes. While polycystin-1 may mediate the contact among cells or between cells and the extracellular matrix, a lot of evidence suggests that polycystin-2 represents an endoplasmic reticulum-bound cation channel. Cyst development has been compared to the growth of benign tumors and this view is highlighted by the model that a somatic mutation in addition to the germline mutation is responsible for cystogenesis (two-hit model of cyst formation). Since in vitro polycystin-1 and polycystin-2 interact through their COOH termini, the two proteins possibly act in a common pathway, which controls the width of renal tubules. The loss of one protein may lead to a disruption of this pathway and to the uncontrolled expansion of tubules. Our increasing knowledge of the molecular events in ADPKD has also started to be useful in designing novel diagnostic and therapeutic strategies.

Key words.PKD1; PKD2; polycystin-1; polycystin-2; ADPKD; polycystic kidney disease. 

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Copyright information

© Birkhäuser Verlag, 2002

Authors and Affiliations

  • A. R. Gallagher
    • 1
  • S. Hidaka
    • 1
  • N. Gretz
    • 2
  • R. Witzgall
    • 1
  1. 1.Institute for Anatomy and Cell Biology I, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg (Germany), Fax: +49 6221 544951, e-mail: ralph.witzgall@urz.uni-heidelberg.de DE
  2. 2.Medical Research Center, Klinikum Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany)DE

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