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

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

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Blotting, Western
  • Cell Membrane / metabolism*
  • Dishevelled Proteins
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Female
  • Fluorescent Antibody Technique
  • Glycogen Synthase Kinase 3 / metabolism*
  • Phosphoproteins / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Dishevelled Proteins
  • Drosophila Proteins
  • Phosphoproteins
  • Receptors, Cell Surface
  • Wnt Proteins
  • arr protein, Drosophila
  • beta Catenin
  • Glycogen Synthase Kinase 3

Grants and funding

This work was supported by an Academic Research Fund (AcRF) grant (MOE2014-T2-2-039) of the Ministry of Education, Singapore to N. Tolwinski. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.