Frizzled

Frizzled is a family of Wnt receptors found in animals. They are seven-pass transmembrane proteins that resemble G protein-coupled receptors. They bind Wnt ligands and initiate Wnt signaling.

In humans there are 10 FZD genes (FZD1–FZD10). Each receptor contains an extracellular cysteine-rich domain (CRD) that binds Wnt ligands, followed by seven transmembrane helices and a cytoplasmic C-terminal tail that interacts with Dishevelled (DVL). Signaling can proceed via canonical (β-catenin) pathway when co-receptors LRP5/6 are engaged, leading to β-catenin stabilization and transcription; and non-canonical pathways such as planar cell polarity (PCP) and Wnt/Ca2+ that do not require β-catenin.

Frizzled receptors regulate cell fate, proliferation, migration, and polarity during embryogenesis and in adult tissue homeostasis. In Drosophila, Frizzled mediates Wingless signaling essential for patterns; in vertebrates, different FZDs show tissue-specific expression and ligand affinities.

Mutations or misregulation of Frizzled signaling are implicated in developmental disorders and cancer; expression changes are seen in various tumors. Frizzled antagonists such as secreted frizzled-related proteins (SFRPs) and other modulators can inhibit signaling by sequestering Wnt ligands or by receptor interactions.

The name Frizzled comes from a Drosophila wing phenotype in which orientation of wing hairs appears frizzled when Wingless signaling is disrupted.