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Article
Nature Cell Biology  4, 191 - 197 (2002)
Published online: 18 February 2002; | doi:10.1038/ncb754

Polycystin-2 is an intracellular calcium release channel

Peter Koulen1, 2, 6, Yiqiang Cai3, 7, Lin Geng3, 7, Yoshiko Maeda3, Sayoko Nishimura3, Ralph Witzgall5, Barbara E. Ehrlich1, 2 & Stefan Somlo3, 4

1  Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA

2  Department of Cellular & Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA

3  Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA

4  Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA

5  Institute of Anatomy and Cell Biology, University of Heidelberg, 69120, Heidelberg, Germany.

6  Present address: Department of Pharmacology and Neuroscience, University of North Texas Health Science, 3500 Camp Bowie Boulevard, Fort Worth, Texas, 76107, USA

7  These authors contributed equally to this work and are listed alphabetically..

Correspondence should be addressed to Stefan Somlo stefan.somlo@yale.edu
Polycystin-2, the product of the gene mutated in type 2 autosomal dominant polycystic kidney disease (ADPKD), is the prototypical member of a subfamily of the transient receptor potential (TRP) channel superfamily, which is expressed abundantly in the endoplasmic reticulum (ER) membrane. Here, we show by single channel studies that polycystin-2 behaves as a calcium-activated, high conductance ER channel that is permeable to divalent cations. Epithelial cells overexpressing polycystin-2 show markedly augmented intracellular calcium release signals that are lost after carboxy-terminal truncation or by the introduction of a disease-causing missense mutation. These data suggest that polycystin-2 functions as a calcium-activated intracellular calcium release channel in vivo and that polycystic kidney disease results from the loss of a regulated intracellular calcium release signalling mechanism.

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REFERENCE
Polycystic Disease of the Kidney
Nature Encyclopaedia of Life Sciences

REVIEWS
Autosomal dominant polycystic kidney disease (ADPKD, MIM 173900, PKD1 and PKD2 genes, protein products known as polycystin-1 and polycystin-2)
European Journal of Human Genetics Reviews (01 May 2004)
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NEWS AND VIEWS
The ins and outs of polycystin-2 as a calcium release channel
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RESEARCH
Cardiac defects and renal failure in mice with targeted mutations in Pkd2
Nature Genetics Letters (01 Jan 2000)
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Nature Cell Biology
ISSN: 1465-7392
EISSN: 1476-4679
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