Figure 1.

Expression of xbp-1s in Neurons or the Intestine Restores Proteostasis in Models of Proteotoxicity

(A) Proteotoxicity and UPR^ER models used in this study. TS, temperature sensitive. ^∗dyn-1(ky51) and let-60(ga89) are expressed in multiple tissues, but their functions in motor neurons and intestine, respectively, are assayed here.

(B) Chemotaxis ability in animals expressing Aβ_1–42 in neurons, with and without neuronal, intestinal, or muscle xbp-1s. Graphs represent mean chemotaxis index ± SD. N = 80–150 animals per assay; each assay was independently replicated 3 times. Significance was assessed by one-way ANOVA with Tukey’s multiple comparisons test, ^∗p < 0.05, ^∗∗∗∗p < 0.0001.

(C) Chemotaxis ability in animals expressing polyQ₄₀::YFP in neurons, with and without neuronal, intestinal, or muscle xbp-1s. Graphs represent mean chemotaxis index ± SD. N = 80–150 animals per assay; each assay was independently replicated 3 times. Significance was assessed by one-way ANOVA with Tukey’s multiple comparisons test, ^∗∗∗∗p < 0.0001.

(D) Paralysis in dyn-1(ky51) animals at 20°C, with and without neuronal xbp-1s. Animals exhibiting body paralysis were counted daily and the paralyzed fraction of the population plotted against time. N = 100 worms per assay; each assay was repeated 3 times.

(E) Prevalence of osmoregulatory defects in let-60(ga89) and wild-type animals, with and without rab-3p::xbp-1s. Animals were placed in distilled water at day 2 of adulthood, and a swollen body after 5 min was scored as osmoregulation defective (Osm). Data represent mean ± SD of 20–25 animals per strain in 3 independent replicates. Significance assessed by two-way ANOVA with Tukey’s multiple comparison, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001.

(F) Paralysis in animals expressing Aβ_1–42 in body wall muscle cells, with and without tissue-specific xbp-1s. Animals exhibiting body paralysis were counted daily and the paralyzed fraction plotted against time. N = 100 worms per assay; each assay was repeated 3 times.

(G) Motility in animals expressing polyQ₃₅::YFP in body wall muscle cells, with and without tissue-specific xbp-1s. Plots represent swimming rate, normalized to N2 day 1 ± SD. N = 30–40 animals per assay; each assay was independently replicated 3 times. Significance was assessed by one-way ANOVA with Tukey’s multiple comparisons test, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001.

(H) Paralysis in populations of unc-15(e1402) animals at 20°C, with and without neuronal xbp-1s. Animals exhibiting body paralysis were counted daily and the paralyzed fraction plotted against time. N = 100 worms per assay; each assay was repeated 3 times.

(I) Muscle fiber organization in wild-type and unc-15(e1402) animals grown at 20°C, with and without neuronal xbp-1s. Muscle cells were visualized using F-actin staining at day 5 of adulthood. Scale bar, 10 μm.