C-terminal domain swapping between FZD4 and FZD6. (A) Schematic presentation of the exchange strategy of the C termini between FZD4 and FZD6, resulting in FZD4-6 C-terminal tail and FZD6-4 C-terminal tail. (B) The primary structure of human FZD4 and FZD6. Green highlights the conserved KTxxxW sequence involved in DVL binding on the presumptive helix 8. Bold marks the terminal PDZ ligand domain. dcFRAP experiments in HEK293T cells coexpressing FZD4-6-GFP and Gα12-mCherry, FZD4-6-mCherry and Gαi1-GFP, or FZD4-6-mCherry and Gαq-Venus (C) and FZD6-4-GFP and Gα12-mCherry, FZD6-4-mCherry and Gαi1-GFP, or FZD6-4-mCherry and Gαq-Venus (D) reveal predominant assembly with Gα12 of the chimeric receptors. ***P < 0.001 (n = 3). Bar graphs show the mean ± S.E.M. PDZ, PSD-95/dics large/ZO-1 homologous.