Figure 7: The dtau mediates the toxic effects of APP/Aβ-42 and the direct modifiers of PAR-1. | Nature Communications

Figure 7: The dtau mediates the toxic effects of APP/Aβ-42 and the direct modifiers of PAR-1.

From: Phospho-dependent ubiquitination and degradation of PAR-1 regulates synaptic morphology and tau-mediated Aβ toxicity in Drosophila

Figure 7

(a,b) Quantification of NMJ bouton number showing rescue by htauS2A (a) or dtau-RNAi (b) of the bouton-loss phenotypes induced by manipulations of the expression APP/Aβ–42 or the PAR-1 ubiquitination modifiers. N indicates the number of animals analysed. The error bars represent mean±s.e.m. P-values were determined using two-tailed Student’s t-test for each comparison. Experiments were performed in triplicate. (c) Genetic interaction between tau and the modifiers of PAR-1 in the retina. Eye images of female flies are shown. All flies were grown at 22 °C. The genotypes are: GMR-Gal4>UAS-htauS2A (n=16), GMR-Gal4>FAFEP381 +UAS-Slimb-ΔF (n=16), GMR-Gal4>UAS-htauS2A+ FAFEP381+UAS-Slimb-ΔF (n=17), GMR-Gal4>UAS-htauM (n=17), GMR-Gal4>UAS-htauM+ FAFEP381+UAS-Slimb-ΔF (n=18) and GMR-Gal4>UAS-htauM +FAFEP381+ UAS-Slimb-ΔF +UAS-PAR-1-RNAi (n=18). Statistically significant differences are P<0.001 (GMR-Gal4>FAFEP381+UAS-Slimb-ΔF, GMR-Gal4>htauS2A+FAFEP381+UAS-Slimb-ΔF; GMR-Gal4>UAS-htauM, GMR-Gal4>UAS-htauM+FAFEP381+UAS-Slimb-ΔF; GMR-Gal4>UAS-htauM+FAFEP381+UAS-Slimb-ΔF, GMR-Gal4>UAS-htauM+FAFEP381+UAS-Slimb-ΔF+UAS-PAR-1-RNAi) as determined by Student’s t-test. Experiments were performed in triplicate. Dashed lines outline the eye contour. Values represent areas of retinal surface normalized with GMR-Gal4/+control. Scale bar, 100 μm. (d) A model depicting the possible signalling pathways linking APP/Aβ–42 to synaptic dysfunction and synapse loss seen in AD. Dashed lines indicate potential direct regulations. n.s, not significant; UPS, Ubiquitin-proteasome system.

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