Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways

Matias Simons, Joachim Gloy, Athina Ganner, Axel Bullerkotte, Mikhail Bashkurov, Corinna Krönig, Bernhard Schermer, Thomas Benzing, Olga A. Cabello, Andreas Jenny, Marek Mlodzik, Bozena Polok, Wolfgang Driever, Tomoko Obara, Gerd Walz

Research output: Contribution to journalArticle

534 Citations (Scopus)

Abstract

Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development.

Original languageEnglish (US)
Pages (from-to)537-543
Number of pages7
JournalNature Genetics
Volume37
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

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Wnt Signaling Pathway
Cystic Kidney Diseases
Kidney
Genes
Cysts
Epithelial Cells
Situs Inversus
Mutation
Cilia
Xenopus laevis
Zebrafish
Renal Insufficiency
Proteins
Embryonic Structures

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Simons, M., Gloy, J., Ganner, A., Bullerkotte, A., Bashkurov, M., Krönig, C., ... Walz, G. (2005). Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nature Genetics, 37(5), 537-543. https://doi.org/10.1038/ng1552

Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. / Simons, Matias; Gloy, Joachim; Ganner, Athina; Bullerkotte, Axel; Bashkurov, Mikhail; Krönig, Corinna; Schermer, Bernhard; Benzing, Thomas; Cabello, Olga A.; Jenny, Andreas; Mlodzik, Marek; Polok, Bozena; Driever, Wolfgang; Obara, Tomoko; Walz, Gerd.

In: Nature Genetics, Vol. 37, No. 5, 05.2005, p. 537-543.

Research output: Contribution to journalArticle

Simons, M, Gloy, J, Ganner, A, Bullerkotte, A, Bashkurov, M, Krönig, C, Schermer, B, Benzing, T, Cabello, OA, Jenny, A, Mlodzik, M, Polok, B, Driever, W, Obara, T & Walz, G 2005, 'Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways', Nature Genetics, vol. 37, no. 5, pp. 537-543. https://doi.org/10.1038/ng1552
Simons, Matias ; Gloy, Joachim ; Ganner, Athina ; Bullerkotte, Axel ; Bashkurov, Mikhail ; Krönig, Corinna ; Schermer, Bernhard ; Benzing, Thomas ; Cabello, Olga A. ; Jenny, Andreas ; Mlodzik, Marek ; Polok, Bozena ; Driever, Wolfgang ; Obara, Tomoko ; Walz, Gerd. / Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. In: Nature Genetics. 2005 ; Vol. 37, No. 5. pp. 537-543.
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