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Fig. 2 | Molecular Brain

Fig. 2

From: Endosomal traffic and glutamate synapse activity are increased in VPS35 D620N mutant knock-in mouse neurons, and resistant to LRRK2 kinase inhibition

Fig. 2

Accumulation of VPS35- FAM21 co-clusters and Rab 11 clusters in VKI dendrites. AD Cultured cortical neurons were immunostained for MAP2 (blue), VPS35 (cyan), and VPS26, FAM21, NEEP21, or Rab11 (magenta) A VPS35 and VPS26 (i); There was no genotype effect on dendritic cluster density of VPS35 (ii, Kruskal–Wallis p = 0.30). VPS26 cluster density was significantly reduced in both mutants (iii, Kruskal–Wallis p < 0.04; Uncorrected Dunn’s Het *p < 0.04 & Ho *p < 0.02), yet there was no genotype effect on co-cluster density or Pearson’s coefficient (iv & v, Kruskal–Wallis p = 0.45 & 0.10, respectively). B VPS35 and FAM21 (i); there was no genotype effect on FAM21 cluster density (ii, Kruskal–Wallis p = 0.24) or Pearson’s coefficients (iv, 1-way ANOVA p = 0.24). There was a significant genotype effect on co-cluster density due to increases in homozygous cells (iii, Kruskal–Wallis p < 0.03; Uncorrected Dunn’s Ho *p < 0.02). C NEEP21 and VPS35 (i); there was no genotype effect on NEEP21 cluster (ii, Kruskal–Wallis p = 0.37) or co-cluster density (iii, Kruskal–Wallis p = 0.38), but a significant genotype effect on Pearson’s coefficient due to a significant reduction in homozygous VKI dendrites (iv, Welch’s ANOVA p < 0.03; Unpaired t with Welch’s correction Ho *p < 0.02). D VPS35 and Rab11 (i); Rab11 cluster density was increased in both genotypes (ii, 1-way ANOVA p < 0.03; Uncorrected Fisher’s LSD *p < 0.02 & *p < 0.03). There was no genotype effect on co-cluster density (iii, 1-way ANOVA p = 0.92), but a significant genotype effect in the Pearson’s coefficient due to reduced correlation in heterozygous dendrites (iv, Welch’s ANOVA p < 0.009; Unpaired t with Welch’s correction Het **p < 0.003)

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