Fig. 2

Inhibitors and activators of the Wnt/β-catenin pathway. A Inhibitors of the Wnt/β-catenin signalling pathway. sFRPs, WIF, Tiki, and Notum are located outside the plasma membrane and inhibit Wnt signal transduction by interacting with Wnts. FZD, LRP5/6, RNF43/ZNRF3, Krem-1/2, ROR, RYK, and glypican are located on the plasma membrane. RNF43/ZNRF3 binds to the FZD receptor complex and induces its ubiquitination and endocytosis. ROR, RYK, and glypican bind to Wnts and inhibit Wnt signal transduction. DKK1/3/4 binds to LRP5/6 or further forms a complex with Krem-1/2 to induce endocytosis. Groucho is located in the nucleus and inhibits the transcription of target genes by binding to LEF. B Activators of the Wnt/β-catenin signalling pathway. R-spondin and Norrin are located outside the plasma membrane. FZD, LRP5/6, RNF43/ZNRF3, and LGR4/5 are located on the plasma membrane. The β-catenin destruction complex (comprising axin, APC, GSK-3β, CK-1α, and β-catenin) and PP2A are located in the cytoplasm. TCF/LEF is located in the nucleus. Association of LGR4/5 and RNF43/ZNRF3 with R-spondin induces membrane retention of FZD. Norrin activates signal transduction by acting as a mimic of Wnts. PP2A dephosphorylates β-catenin to promote the accumulation of β-catenin in the cytoplasm. Β-catenin enters the nucleus and combines with TCF/LEF to initiate the transcription of target genes. DKK Dickkopf, WIF Wnt inhibitory factor, CRD cysteine-rich domain, LRP lipoprotein receptor-related protein, RNF ring finger protein