ZFIN ID: ZDB-PUB-150114-1
Down syndrome critical region protein 5 regulates membrane localization of Wnt receptors, Dishevelled stability and convergent extension in vertebrate embryos
Shao, M., Liu, Z.Z., Wang, C.D., Li, H.Y., Carron, C., Zhang, H.W., and Shi, D.L.
Date: 2009
Source: Development (Cambridge, England)   136(12): 2121-31 (Journal)
Registered Authors: Li, Hongyan
Keywords: none
MeSH Terms:
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Caveolins/physiology
  • Cell Membrane/metabolism*
  • Embryo, Nonmammalian/physiology
  • Endocytosis
  • Glypicans/metabolism
  • Heparan Sulfate Proteoglycans/metabolism
  • Humans
  • Membrane Proteins/genetics
  • Membrane Proteins/physiology*
  • Mutation
  • N-Acetylglucosaminyltransferases/genetics
  • N-Acetylglucosaminyltransferases/physiology*
  • Phosphoproteins/metabolism*
  • Receptors, Cell Surface/metabolism*
  • Receptors, G-Protein-Coupled/metabolism
  • Signal Transduction
  • Ubiquitination
  • Wnt Proteins/metabolism*
  • Xenopus Proteins/genetics
  • Xenopus Proteins/metabolism
  • Xenopus Proteins/physiology*
  • Xenopus laevis
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Zebrafish Proteins/physiology*
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.