Fig. 1. Canonical and non-canonical Frizzled signalling pathways. (A) A simplified scheme of the canonical Wnt signalling pathway. In this pathway, a Wnt ligand binds to a Frizzled (Fz) family receptor and a co-receptor of the low density lipoprotein receptor-related protein (LRP) family. In canonical Wnt pathways, Dishevelled (Dsh) and ß-catenin are characteristically required to transduce the Wnt signal, leading to a transcriptional response mediated by transcription factors of the ternary complex factor (TCF)/lymphoid enhancer factor 1 (LEF1) family. Fz receptors might also couple to heterotrimeric G proteins in this pathway (see text for more details). (B) Planar polarity involves a non-canonical ß-catenin-independent Wnt/Fz pathway that requires Dsh. A Wnt ligand for this pathway has yet to be identified in Drosophila ('?'), although Wnt ligands have been found to activate an analogous pathway in vertebrates. There is also no evidence, as yet, for heterotrimeric G proteins being involved. This pathway involves the core planar polarity proteins (blue) Flamingo/Starry Night (Fmi/Stan), Van Gogh/Strabismus (Vang/Stbm), Prickle (Pk) and Diego (Dgo). These proteins are thought to modulate the activity of this pathway by forming a multiprotein complex with Fz/Dsh that spans cell-cell junctions, rather than being cascade components. Fmi/Stan and Vang/Stbm are both multipass transmembrane proteins, whereas Pk and Dgo are cytoplasmic proteins. The prickle (pk) locus produces two protein isoforms, Pk and Spiny Legs (Sple), which vary in activity from tissue to tissue (only Pk is shown here for simplicity). (C) The Wnt/Ca²⁺ pathway probably signals via heterotrimeric G-proteins (, ß, subunits), to mobilise intracellular Ca²⁺ and, in some contexts, to stimulate protein kinase C (PKC). Whether this pathway requires Dsh remains controversial (see text for more details). In vertebrates, Wnt/Ca²⁺ signalling is activated by the same ligands as the planar polarity pathway, suggesting that these pathways may overlap to some extent.

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