The complex world of WNT receptor signalling

Nat Rev Mol Cell Biol. 2012 Dec;13(12):767-79. doi: 10.1038/nrm3470. Epub 2012 Nov 15.


30 years after the identification of WNTs, their signal transduction has become increasingly complex, with the discovery of more than 15 receptors and co-receptors in seven protein families. The recent discovery of three receptor classes for the R-spondin family of WNT agonists further adds to this complexity. What emerges is an intricate network of receptors that form higher-order ligand-receptor complexes routing downstream signalling. These are regulated both extracellularly by agonists such as R-spondin and intracellularly by post-translational modifications such as phosphorylation, proteolytic processing and endocytosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Drosophila melanogaster / metabolism
  • Endocytosis
  • Female
  • Heparan Sulfate Proteoglycans / metabolism
  • Humans
  • Male
  • Mice
  • Protein Processing, Post-Translational
  • Receptor Tyrosine Kinase-like Orphan Receptors / metabolism
  • Receptors, Wnt / physiology*
  • Thrombospondins / metabolism
  • Wnt Proteins / physiology
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism


  • Heparan Sulfate Proteoglycans
  • Receptors, Wnt
  • Thrombospondins
  • Wnt Proteins
  • beta Catenin
  • Receptor Tyrosine Kinase-like Orphan Receptors