Fig. 7

FTI treatment enhances retrograde lysosomal trafficking in mouse primary forebrain neurons. Wild-type primary forebrain neurons were grown for seven days in culture and treated for 48 hours with vehicle (DMSO), 10 nM LNK-754 or 10 nM lonafarnib. A Representative images showing Lysotracker Green fluorescence (black puncta) in wild-type primary forebrain neurons. Arrows denote cell bodies. Scale bar, 50 μm. B Kymographs of vehicle (n = 25), LNK-754 (n = 28) and lonafarnib (n = 26)-treated wild-type primary forebrain neurons. Quantifications of the frequency distribution of LT vesicle movement (for stationary particles, *p = 0.046 between vehicle and lonafarnib, for retrograde particles, ***p = 0.0007 between vehicle and LNK-754, and ***p = 0.0005 between vehicle and lonafarnib) (C) and number of LT vesicles per axon length (*p = 0.040 between vehicle and lonafarnib) (D). Quantifications of LT vesicle distance (in exp. 1, ***p = 0.004 between vehicle and LNK-754, ****p < 0.001 between vehicle and lonafarnib, in exp. 2, **p = 0.0012 between vehicle and LNK-754, ****p < 0.0001 between vehicle and lonafarnib) (E, G) and speed (in exp. 1, ***p = 0.0004 between vehicle and LNK-754, ****p < 0.0001 between vehicle and lonafarnib, in exp. 2, ***p = 0.0001 between vehicle and LNK-754, ****p < 0.0001 between vehicle and lonafarnib) (F, H) traveled (n = 2 experiments, 15–20 replicates analyzed per group). Each data point corresponds to the mean speed or distance of LT particle movement in neurons treated with vehicle, LNK-754 or lonafarnib per replicate in each experiment. 1-way ANOVA with Tukey’s post-hoc multiple comparisons test was performed