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Fig. 6 | Molecular Neurodegeneration

Fig. 6

From: Pathogenic LRRK2 variants are gain-of-function mutations that enhance LRRK2-mediated repression of β-catenin signaling

Fig. 6

Effect of LRRK2 mutations on basal Wnt signalling. Lrrk2 knockout (KO) cells were transfected with TOPflash or FOPflash plus wild-type LRRK2 or the indicated LRRK2 mutant. a 1-way ANOVA (n = 9-15, F = 3.296, p < 0.05) followed by 2-sided Dunnett’s post-hoc analysis indicate that pathogenic LRRK2 mutations weaken canonical Wnt signalling relative to wild-type LRRK2 (RG, p < 0.05; YC, p < 0.05; GS, p < 0.05). RC is decreased relative to wild-type but does not reach significance. b 1-way ANOVA (n = 9, F = 13.388, p < 0.001) followed by 2-sided Dunnett’s post-hoc analysis indicate the pathogenic LRRK2 mutation GR weakens basal canonical Wnt signalling relative to wild-type LRRK2 (p < 0.01), whilst the protective RH mutation enhances canonical Wnt activity (p < 0.01). Note that the pathogenic mutations NH and RP decreased relative to wild-type but neither reaches significance. Mutations used: RC = R1441C, RG = R1441G, YC = Y1699C, GS = G2019S, NH = N1437H, RP = R1628P, GR = G2385R; RH = R1398H

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Molecular Neurodegeneration

ISSN: 1750-1326