CRD motif and sFRPs influence on Wnt signaling (Danio rerio)

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Wnt signaling plays a crucial role in embryogenesis as well as in adult stem cell regulation and cancer.

The Wnt signaling cascade is initiated by binding of secreted Wnt proteins to seven-pass transmembrane Fz receptors and diverse co-receptors. The extracellular CRD of Fz family members thereby serves as a highly conserved binding site for Wnt ligands.

When expressed alone, Fz7 or Ror2 receptors activate distinct non-canonical Wnt pathways stimulated by Wnt5a. When sFRP2 is present, Fz7 receptor endocytosis is prevented, and Fz7 signaling is inhibited, whereas Ror2 signaling is enhanced indicated by stabilized Wnt5a-Ror2 membrane complexes.

When both receptors are present in the same cell, the Ror2-CRD acts in a similar way as sFRP2, leading to increased Ror2 activation at the expense of Fz7 signaling.

 

Study conducted on wild-type zebrafish AB2O3.