Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells

Surya M. Nauli, Francis J. Alenghat, Ying Luo, Eric Williams, Peter Vassilev, Xiaogang Li, Andrew E.H. Elia, Weining Lu, Edward M. Brown, Stephen J. Quinn, Donald E. Ingber, Jing Zhou

Research output: Contribution to journalArticle

1386 Citations (Scopus)

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 polycystin-1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by Pkdl 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 Ca2+ influx in response to physiological fluid flow. Blocking antibodies directed against PC2 similarly abolished the flow response in wild-type cells as did inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins, phospholipase C and InsP3 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.

Original languageEnglish (US)
Pages (from-to)129-137
Number of pages9
JournalNature Genetics
Volume33
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

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Cilia
Polycystic Kidney Diseases
Kidney
Epithelium
Autosomal Dominant Polycystic Kidney
Ryanodine Receptor Calcium Release Channel
Blocking Antibodies
Type C Phospholipases
Protein C
Morphogenesis
GTP-Binding Proteins
Transgenic Mice
Cues
Cysts
Proteins
polycystic kidney disease 2 protein
polycystic kidney disease 1 protein
Mutation
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Nauli, S. M., Alenghat, F. J., Luo, Y., Williams, E., Vassilev, P., Li, X., ... Zhou, J. (2003). Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nature Genetics, 33(2), 129-137. https://doi.org/10.1038/ng1076

Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. / Nauli, Surya M.; Alenghat, Francis J.; Luo, Ying; Williams, Eric; Vassilev, Peter; Li, Xiaogang; Elia, Andrew E.H.; Lu, Weining; Brown, Edward M.; Quinn, Stephen J.; Ingber, Donald E.; Zhou, Jing.

In: Nature Genetics, Vol. 33, No. 2, 01.02.2003, p. 129-137.

Research output: Contribution to journalArticle

Nauli, SM, Alenghat, FJ, Luo, Y, Williams, E, Vassilev, P, Li, X, Elia, AEH, Lu, W, Brown, EM, Quinn, SJ, Ingber, DE & Zhou, J 2003, 'Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells', Nature Genetics, vol. 33, no. 2, pp. 129-137. https://doi.org/10.1038/ng1076
Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nature Genetics. 2003 Feb 1;33(2):129-137. https://doi.org/10.1038/ng1076
Nauli, Surya M. ; Alenghat, Francis J. ; Luo, Ying ; Williams, Eric ; Vassilev, Peter ; Li, Xiaogang ; Elia, Andrew E.H. ; Lu, Weining ; Brown, Edward M. ; Quinn, Stephen J. ; Ingber, Donald E. ; Zhou, Jing. / Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. In: Nature Genetics. 2003 ; Vol. 33, No. 2. pp. 129-137.
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