Specificity of WNT-receptor interactions

The highly conserved Wnt signaling proteins play critical roles in guiding pattern formation, cell fate decision, and morphogenetic movement during animal development. They bind to the Frizzled family of seven-pass transmembrane proteins and initiate at least three different intracellular signaling pathways, resulting in regulation of gene expression and/or changes in cell behavior. A single transmembrane protein from the low-density-lipoprotein family functions as a co-receptor in the canonical/beta-catenin pathway. The specificity of Wnt signaling depends in part on the affinities between various Wnt-Frizzled pairs. A Wnt-dependent receptor dimerization or clustering step has been hypothesized as the step that initiates the canonical signaling cascade in cells.