Fig. 2

Tissue-specific expression of MATR3 leads to progressive degeneration in motor neurons and muscles. a Kaplan–Meier survival curve in flies constitutively expressing MATR3 in motor neurons, driven by OK371-Gal4, and b in muscles, driven by MHC-Gal4. Expression of MATR3 WT and mutants in either tissue moderately, but significantly, reduced longevity of the flies compared to driver-alone control (n = 100; Log-Rank Mantel-Cox test). c Quantification of the percent flies that can climb and d average velocity at which they climb at day-2, day-15 and day-30 of adult lifespan (n = 50; One-way ANOVA), e H&E stained indirect flight muscles in transverse thoracic cross-sections in 30-day old flies expressing MATR3 in muscles. Red arrows indicate enlarged gaps between muscle fibers in the S85C and F115C-expressing flies indicating muscle degeneration. f Quantification of the cross-sectional area of dorsal-longitudinal muscle (DLM) segments 1, 2 and 3. DLMs of MATR3-expressing flies showed lower cross-sectional area compared to driver-alone control, with F115C and S85C flies exhibiting more pronounced atrophy (n = 4 hemi-segments per group; One-way ANOVA). g Immunoblot showing the NP40-soluble and NP40-insoluble fractions of MATR3 in Drosophila thorax lysates from flies expressing MATR3 in muscles. h Quantification of insoluble/soluble MATR3 protein fraction. S85C mutant protein is significantly more enriched in the insoluble fraction (n = 4-6 per group; One-way ANOVA). α-tubulin is used as loading control. i Quantification of insoluble/soluble MATR3 protein fraction at day-1 and day-20 of adult fly lifespan. MATR3 WT, F115C and S85C are significantly more enriched in the insoluble fraction at day-20 compared to day-1. MATR3-S85C at day-20 is significantly more enriched in the insoluble fraction compared to WT and F115C at day-20 (n = 4-6 per group; One-way ANOVA). Error bars indicate S.E.M. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001