A finger on the pulse of Wnt receptor signaling

Cell Res. 2012 Oct;22(10):1410-2. doi: 10.1038/cr.2012.91. Epub 2012 Jun 12.

Abstract

In a recent issue of Nature, Hao et al. report an unexpected link between the secreted stem cell factor/Wnt agonist R-spondin and Wnt receptors through the transmembrane ZNRF3 protein, a RING finger ubiquitin ligase. ZNRF3 acts to turn over Frizzled and LRP6 receptors. R-spondin binds to ZNRF3, in addition to transmembrane LGR4/5 receptors, to antagonize degradation of the Wnt receptors by ZNRF3, thereby resulting in increased Frizzled and LRP6 levels and a greater Wnt response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Frizzled Receptors / metabolism
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-6 / metabolism
  • Protein Binding
  • RNA Interference
  • Receptors, Wnt / metabolism*
  • Stem Cell Factor / metabolism
  • Thrombospondins / metabolism
  • Ubiquitin-Protein Ligases / antagonists & inhibitors
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Wnt Proteins / agonists
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway*

Substances

  • Frizzled Receptors
  • LRP6 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-6
  • RSPO1 protein, human
  • Receptors, Wnt
  • Stem Cell Factor
  • Thrombospondins
  • Wnt Proteins
  • Ubiquitin-Protein Ligases
  • ZNRF3 protein, human