Inhibitors of endocytosis prevent Wnt/Wingless signalling by reducing the level of basal β-catenin/Armadillo

J Cell Sci. 2014 Nov 15;127(Pt 22):4918-26. doi: 10.1242/jcs.155424. Epub 2014 Sep 18.


A key step in the canonical Wnt signalling pathway is the inhibition of GSK3β, which results in the accumulation of nuclear β-catenin (also known as CTNNB1), and hence regulation of target genes. Evidence suggests that endocytosis is required for signalling, yet its role and the molecular understanding remains unclear. A recent and controversial model suggests that endocytosis contributes to Wnt signalling by causing the sequestration of the ligand-receptor complex, including LRP6 and GSK3 to multivesicular bodies (MVBs), thus preventing GSK3β from accessing β-catenin. Here, we use specific inhibitors (Dynasore and Dyngo-4a) to confirm the essential role of endocytosis in Wnt/Wingless signalling in human and Drosophila cells. However, we find no evidence that, in Drosophila cells or wing imaginal discs, LRP6/Arrow traffics to MVBs or that MVBs are required for Wnt/Wingless signalling. Moreover, we show that activation of signalling through chemical blockade of GSK3β is prevented by endocytosis inhibitors, suggesting that endocytosis impacts on Wnt/Wingless signalling downstream of the ligand-receptor complex. We propose that, through an unknown mechanism, endocytosis boosts the resting pool of β-catenin upon which GSK3β normally acts.

Keywords: Endocytosis; Signalling; Wnt; β-catenin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Armadillos
  • Drosophila
  • Endocytosis / physiology*
  • Humans
  • Signal Transduction
  • Wnt1 Protein / metabolism*
  • beta Catenin / metabolism*


  • Wnt1 Protein
  • beta Catenin