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Fig. 2 | Acta Neuropathologica Communications

Fig. 2

From: A metastable subproteome underlies inclusion formation in muscle proteinopathies

Fig. 2

Proteins in rimmed vacuoles from protein aggregation myopathies are supersaturated. Representative images of: (a) healthy control myofibers (HC), control unaffected myofibers in diseased samples (DC), surrounding tissues of affected fibers (AF), and rimmed vacuoles (RV) from human subjects with inclusion body myositis, and (c) DC and AF samples from human subjects with myotilin mutations. Outlines represent areas for LMD. In (c), prior to LMD, muscle was immunostained with an antibody directed to myotilin (green) to identify aggregate containing fibers (AF). b, d, e Comparison of the unfolded supersaturation scores (σu) of the proteome (Prt) (N = 15,954) and (b) proteins enriched in RVs (RV) (N = 50), amyloid plaques (Plq) (N = 26), neurofibrillary tangles (NFT) (N = 76), proteins found in TDP-43 inclusions (TDP) (N = 32); (d) proteins enriched in affected fibers from any of three protein aggregation myopathies (hPAM) (N = 50); and (e) proteins enriched in affected fibers from individual protein aggregation myopathies involving desmin (Desm) (N = 6), filamin (Fil) (N = 16), and myotilin (Myot) (N = 46) mutations. f, g Comparison of the folded supersaturation scores (σf) for the proteome (Prt) (N = 1605) and (f) the proteins enriched in affected fibers from any of three protein aggregation myopathies (hPAM) (N = 46) and (g) the proteins enriched in affected fibers from individual protein aggregation myopathies involving desmin (Desm) (N = 5), filamin (Fil) (N = 15), and myotilin (Myot) (N = 43) mutations. The fold change (Δ) represents the fold difference in the median σu or σf scores between each inclusion type and the proteome. The median σu or σf supersaturation score for the proteome is normalized to 0. Boxes range from the 25th percentile to 75th percentile, while whiskers extend to maximum and minimum data points up to 1.5x interquartile range above and below the limits of the boxes. Remaining outliers are plotted as open circles. Statistical significance determined by one-tailed Wilcoxon/Mann-Whitney test with Holm-Bonferroni correction. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001

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