Down syndrome critical region protein 5 regulates membrane localization of Wnt receptors, Dishevelled stability and convergent extension in vertebrate embryos
- Authors
- Shao, M., Liu, Z.Z., Wang, C.D., Li, H.Y., Carron, C., Zhang, H.W., and Shi, D.L.
- ID
- ZDB-PUB-150114-1
- Date
- 2009
- Source
- Development (Cambridge, England) 136(12): 2121-31 (Journal)
- Registered Authors
- Li, Hongyan
- Keywords
- none
- MeSH Terms
-
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Zebrafish Proteins/physiology*
- Receptors, G-Protein-Coupled/metabolism
- Humans
- Xenopus Proteins/genetics
- Xenopus Proteins/metabolism
- Xenopus Proteins/physiology*
- Ubiquitination
- Embryo, Nonmammalian/physiology
- Cell Membrane/metabolism*
- Heparan Sulfate Proteoglycans/metabolism
- N-Acetylglucosaminyltransferases/genetics
- N-Acetylglucosaminyltransferases/physiology*
- Receptors, Cell Surface/metabolism*
- Caveolins/physiology
- Signal Transduction
- Mutation
- Membrane Proteins/genetics
- Membrane Proteins/physiology*
- Xenopus laevis
- Zebrafish
- Glypicans/metabolism
- Animals
- Wnt Proteins/metabolism*
- Endocytosis
- Phosphoproteins/metabolism*
- Adaptor Proteins, Signal Transducing/metabolism*
- PubMed
- 19465602 Full text @ Development
The Glypican family of heparan sulfate proteoglycans regulates Wnt signaling and convergent extension (CE) in vertebrate embryos. They are predicted to be glycosylphosphatidylinositol (GPI)-tethered membrane-bound proteins, but there is no functional evidence of their regulation by the GPI synthesis complex. Down syndrome critical region protein 5 (Dscr5, also known as Pigp) is a component of the GPI-N-acetylglucosaminyltransferase (GPI-GnT) complex, and is associated with specific features of Down syndrome. Here we report that Dscr5 regulates CE movements through the non-canonical Wnt pathway. Both dscr5 overexpression and knockdown impaired convergence and extension movements. Dscr5 functionally interacted with Knypek/Glypican 4 and was required for its localization at the cell surface. Knockdown of dscr5 disrupted Knypek membrane localization and caused an enhanced Frizzled 7 receptor endocytosis in a Caveolin-dependent manner. Furthermore, dscr5 knockdown promoted specific Dishevelled degradation by the ubiquitin-proteosome pathway. These results reveal a functional link between Knypek/Glypican 4 and the GPI synthesis complex in the non-canonical Wnt pathway, and provide the new mechanistic insight that Dscr5 regulates CE in vertebrate embryos by anchoring different Wnt receptors at the cell surface and maintaining Dishevelled stability.