XB-ART-1988
Nat Genet
May 1, 2005;
37
(5):
537-43.
Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways.
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
.
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.
PubMed ID:
15852005
PMC ID:
PMC3733333
Article link:
Nat Genet
Grant support:
[+]
Species referenced:
Xenopus laevis
Genes referenced:
ankrd6
dvl2
invs
GO keywords:
non-canonical Wnt signaling pathway
[+]
Morpholinos:
invs MO1
Disease Ontology terms:
physical disorder
[+]
OMIMs:
NEPHRONOPHTHISIS 2; NPHP2
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