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Membrane trafficking

A GSK3 lockdown

Nature Reviews Molecular Cell Biology volume 12, page 72 (2011)Cite this article

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Taelman et al. observed that WNT-treated cell extracts did not change the overall enzymatic activity of GSK3, suggesting that WNT must regulate GSK3 through another means. It was known that WNT receptor complexes need to be internalized into endosomes for WNT signalling, but the reason for this was unknown. The authors thus hypothesized that, as has been observed for other growth factor receptors, GSK3–WNT receptor complexes might also be internalized and delivered to the lumen of MVBs, thus separating GSK3 from the cytosol.

They tested this hypothesis by asking how WNT affects the subcellular localization of GSK3. Fluorescently labelled Xenopus laevis WNT and GSK3 accumulated together in endosomes and, on WNT3A treatment, GSK3 was protected from proteinase K digestion, suggesting that it localizes to a membrane-bound compartment. Cryoelectron microscopy revealed this compartment to be an MVB. Thus, stimulation of WNT signalling drives GSK3 into MVBs.

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References

ORIGINAL RESEARCH PAPER

  1. Taelman, V. F. et al. Wnt signalling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell 143, 1136–1148 (2010) Article

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FURTHER READING

  1. Angers, S. & Moon, R. T. Proximal events in Wnt signal transduction. Nature Rev. Mol. Cell Biol. 10, 468–477 (2009) Article

    Article  CAS  Google Scholar 

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Authors
  1. Alison Schuldt
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Schuldt, A. A GSK3 lockdown. Nat Rev Mol Cell Biol 12, 72 (2011). https://doi.org/10.1038/nrm3052

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