Fig. 2: DVL modulates WNT-induced FZD₅-LRP6 association.

A Schematic depiction of mutational paradigms. The FZD₅ R^6.32A mutants preferentially signals in DVL-independent fashion. The DVL2 M2/M4 mutant cannot polymerize by its DIX domains. The DVL2 L445E mutant cannot engage FZD via its DEP domain. Created in BioRender. Voss, J. (2025) https://BioRender.com/zfu7r84. B ΔBRET traces of HEK293 cells transfected either with WT FZD₅-Nluc or FZD₅ R^6.32A-Nluc (dark and light blue circles, respectively) and LRP6-Venus, stimulated with 1000 ng/ml WNT-3A. C ΔBRET traces of HEK293 and HEK293T ΔDVL1-3 cells, transfected with FZD₅-Nluc, LRP6-Venus and either pcDNA (green and black circles), DVL2 (cyan and magenta), or DVL2-M2/M4 (dark cyan and purple) as indicated, stimulated with 1000 ng/ml WNT-3A. D ΔBRET traces of ΔDVL1-3 cells, transfected with FZD₅-Nluc, LRP6-Venus and either pcDNA (black), DVL1 (green), DVL2 (magenta), or DVL3 (purple) as indicated, stimulated with 1000 ng/ml WNT-3A. E ΔBRET traces of ΔDVL1-3 cells, transfected with FZD₅-Nluc, LRP6-Venus and either pcDNA (black), DVL2 (magenta), DVL2-M2/M4 (purple), DVL2-L445E (orange), or DVL2-M2/M4-L445E (red) as indicated, stimulated with 1000 ng/ml WNT-3A. F Scheme illustrating a proposed mechanism of DVL modulation of WNT-induced FZD₅-LRP6 interaction. Created in BioRender. Voss, J. (2025) https://BioRender.com/3gct1ez. Data are shown as mean ± SEM of three (B – FZD₅ R^6.32A, C – data with DVL2-M2/M4 co-expression D, E) or four (B – wt FZD₅, C – all other data) individual experiments performed in triplicate. Parts of this figure were created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDrivs 4.0 International license.