Polycystin-2 is an intracellular calcium release channel
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- 18 February 2002
- journal article
- Published by Springer Nature in Nature Cell Biology
- Vol. 4 (3) , 191-197
- https://doi.org/10.1038/ncb754
Abstract
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.Keywords
This publication has 41 references indexed in Scilit:
- The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathwayCurrent Biology, 2001
- Co-assembly of polycystin-1 and -2 produces unique cation-permeable currentsNature, 2000
- Ion Channels and Synaptic OrganizationNeuron, 2000
- Cardiac defects and renal failure in mice with targeted mutations in Pkd2Nature Genetics, 2000
- Somatic Inactivation of Pkd2 Results in Polycystic Kidney DiseaseCell, 1998
- Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutationNature Genetics, 1997
- PKD1 interacts with PKD2 through a probable coiled-coil domainNature Genetics, 1997
- The Molecular Basis of Focal Cyst Formation in Human Autosomal Dominant Polycystic Kidney Disease Type ICell, 1996
- PKD2 , a Gene for Polycystic Kidney Disease That Encodes an Integral Membrane ProteinScience, 1996
- The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16Cell, 1994