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 (FZD) family of seven-pass transmembrane proteins and initiate at least three different intracellular signaling pathways. Historically they were considered to be family B GPCRs but more recent phylogenetic classifications put them into a class of their own (e.g. Schioth & Fredriksson 2005). FZD members have been demonstrated to signal via Gi/o (Slusarski et al. 1997) but this is not considered to be the primary signaling mechanism for these receptors (Hsieh 2004). Instead they signal through the canonical/beta-catenin pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. The canonical/beta-catenin pathway requires a co-receptor protein known as LDL5 or LDL6 (Tamai et al. 2000).
Most Wnt signaling has been attributed to the activation of FZD receptors but there is evidence of FZD-independent signaling (Mikels & Nusse 2006). Much Wnt research has used indirect evidence to infer the involvement of FZD receptors (e.g. Gazit et al. 1999) but there is some direct evidence of Wnt-FZD binding (Hsieh et al. 1999; Mikels & Nusse 2006).