Fig. 7: Restoring TDP-43 localization recovers local translation of mitochondrial proteins in distal axons and the NMJs. | Nature Communications

Fig. 7: Restoring TDP-43 localization recovers local translation of mitochondrial proteins in distal axons and the NMJs.

From: Axonal TDP-43 condensates drive neuromuscular junction disruption through inhibition of local synthesis of nuclear encoded mitochondrial proteins

Fig. 7

a Western-blot and quantification of TDP-43, hTDP-43 levels in sciatic axoplasm of control, TDP∆NLS, and recovered-TDP∆NLS (Rec.). Tubulin was used as loading control. n = 3,3,3 mice. Data are presented as mean values ± SEM. One-way-ANOVA with Holm-Sidak correction. ****p < 0.0001. b Images and c quantification of TDP-43 intensity within ChAT-positive axons in sciatic nerve sections of control, TDP∆NLS, and recovered-TDP∆NLS mice. Scale bar=20 µm. n = 34,34,33 images from 3 mice of each condition. Data are presented as mean values ± SD. One-way-ANOVA with Holm-Sidak correction *p = 0.0412, ****p < 0.0001. d Images and e quantification of the percent of NMJs with apparent TDP-43 condensates in control, TDP∆NLS, and recovered-TDP∆NLS mice. Scale bar=10 µm. n = 3,3,3 mice from each condition. Data are presented as mean values ± SEM. Unpaired-t-test, two-sided ***p = 0.0001. f Images and g analysis of OPP puncta density in in-vitro NMJs of control, TDP∆NLS and Recovered-TDP∆NLS co-cultures. Scale bar=5 µm. n = 3 independent repeats. Data are presented as mean values + SEM. One-way-ANOVA with Holm-Sidak correction. ***p = 0.0004 (left), ***p = 0.0004 (right). h Images and i analysis of the OPP labeling intensity in pre-synaptic NMJs of control, TDP∆NLS and recovered-TDP∆NLS mice. n = 32,30,39 NMJs, from 3,3,3 mice. Scale bar=10 µm. Data are presented as mean values ± SD. One-way-ANOVA with Holm-Sidak correction. *p = 0.019, ***p = 0.0001. j Images and k representative channel histograms of Cox4i and OPP intensities within pre-synaptic axon (ChAT) in NMJs of control TDP∆NLS mice, l–m quantification of Cox4i area (l), and of Cox4i-OPP coloc-area within pre-synaptic axons (ChAT) in NMJs of control, TDP∆NLS, and recovered-TDP∆NLS mice. Scale bar=10 µm. n = 23,21,13 NMJs. 3,3,3 mice. Data are presented as mean values ± SD. One-way-ANOVA with Holm-Sidak correction. ****p < 0.0001, ***p = 0.0007 (l), 0.0002 (m), **p = 0.0027. a.u stands for arbitrary units. f.c stands for Fold Change. Source data are provided as a Source Data file.

Back to article page