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Dev Cell March 15, 2011; 20 (3): 303-14.

Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis.

Ohkawara B , Glinka A , Niehrs C .

The R-Spondin (Rspo) family of secreted Wnt modulators is involved in development and disease and holds therapeutic promise as stem cell growth factors. Despite growing biological importance, their mechanism of action is poorly understood. Here, we show that Rspo3 binds syndecan 4 (Sdc4) and that together they activate Wnt/PCP signaling. In Xenopus embryos, Sdc4 and Rspo3 are essential for two Wnt/PCP-driven processes-gastrulation movements and head cartilage morphogenesis. Rspo3/PCP signaling during gastrulation requires Wnt5a and is transduced via Fz7, Dvl, and JNK. Rspo3 functions by inducing Sdc4-dependent, clathrin-mediated endocytosis. We show that this internalization is essential for PCP signal transduction, suggesting that endocytosis of Wnt-receptor complexes is a key mechanism by which R-spondins promote Wnt signaling.

PubMed ID: 21397842
Article link: Dev Cell

Species referenced: Xenopus
Genes referenced: acss2.2 adam11 cltc dvl2 fzd7 mapk8 rspo3 sdc4 tbxt wnt5a
Morpholinos: ap2m1 MO1 dvl2 MO1 fzd7 MO1 lrp6 MO1 rspo3 MO1 sdc4 MO1 sdc4 MO2 wnt5a MO1

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