Figure 3. Secreted Wnt antagonists and agonists.
A) Antagonists. WIF and sFRP bind directly to secreted Wnts and/or Fz. DKK and SOST/WISE proteins bind LRP5/6 to prevent Fz-LRP6 complex formation. Shisa proteins trap Fz in the ER. B) Agonists. Wnts are the primary agonists and form a complex with LRP5/6 and Fz to activate signaling. Norrin acts similar to Wnt, but binds specifically to Fz4. R-spondin proteins (Rspo) act via and may bind to LRP5/6 and/or Fz receptors. In the ER, the chaperone MESD is needed for LRP5/6 maturation.