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PLoS One. 2015 Apr 7;10(4):e0121879. doi: 10.1371/journal.pone.0121879. eCollection 2015.

Membrane bound GSK-3 activates Wnt signaling through disheveled and arrow.

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Yale-NUS College and Department of Biological Sciences, National University of Singapore, Block MD6, Centre for Translational Medicine, Yong Loo Lin School of Medicine, 14 Medical Drive, Level 10 South, 10-02M, Singapore 117599, Singapore.


Wnt ligands and their downstream pathway components coordinate many developmental and cellular processes. In adults, they regulate tissue homeostasis through regulation of stem cells. Mechanistically, signal transduction through this pathway is complicated by pathway components having both positive and negative roles in signal propagation. Here we examine the positive role of GSK-3/Zw3 in promoting signal transduction at the plasma membrane. We find that targeting GSK-3 to the plasma membrane activates signaling in Drosophila embryos. This activation requires the presence of the co-receptor Arrow-LRP5/6 and the pathway activating protein Disheveled. Our results provide genetic evidence for evolutionarily conserved, separable roles for GSK-3 at the membrane and in the cytosol, and are consistent with a model where the complex cycles from cytosol to membrane in order to promote signaling at the membrane and to prevent it in the cytosol.

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