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- Title
Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells.
- Authors
Nauli, Surya M.; Alenghat, Francis J.; Ying Luo; Williams, Eric; Vassilev, Peter; Xiaogang Li; Elia, Andrew E.H.; Weining Lu; Brown, Edward M.; Quinn, Stephen J.; Ingber, Donald E.; Jing Zhou
- Abstract
Several proteins implicated in the pathogenesis of polycystic kidney disease (PKD) localize to cilia. Furthermore, cilia are malformed in mice with PKD with mutations in TgN737Rpw (encoding polaris). It is not known, however, whether ciliary dysfunction occurs or is relevant to cyst formation in PKD. Here, we show that polycystin1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by Pkd1 and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD, co-distribute in the primary cilia of kidney epithelium. Cells isolated from transgenic mice that lack functional PC1 formed cilia but did not increase Ca[sup 2+] influx in response to physiological fluid flow. Blocking antibodies directed against PC2 similarly abolished the flow response in wildtype cells as did inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins, phospholipase C and InsP[sub 3] receptors had no effect. These data suggest that PC1 and PC2 contribute to fluid-flow sensation by the primary cilium in renal epithelium and that they both function in the same mechanotransduction pathway. Loss or dysfunction of PC1 or PC2 may therefore lead to PKD owing to the inability of cells to sense mechanical cues that normally regulate tissue morphogenesis.
- Subjects
POLYCYSTIC kidney disease; MEMBRANE proteins; KIDNEY tubules
- Publication
Nature Genetics, 2003, Vol 33, Issue 2, p129
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng1076