Figure 5: HDAC6 and Sirt2 RNAi restores axonal transport and locomotion.

(a) Kymographs of mitochondria in transgenic Drosophila motor neurons expressing mito-GFP with indicated LRRK2 variants alone (top) or in combination with HDAC6 or Sirt2 RNAi transgenes. Ctrl RNAi is expressing a lacZ-RNAi transgene. (b) Charts are mean±s.e.m. of quantified mitochondrial transport shown as percentage of total mitochondria. (c) Locomotion assays for climbing behavior of indicated genotypes. Transgene expression is driven by D42-GAL4. Ctrl is driver crossed to a lacZ transgene. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, one-way analysis of variance followed by Fisher’s least significant difference post hoc test. (b) left chart: N (animals)=Ctrl RNAi, 11; R1441C, 9; R1441C+Ctrl RNAi, 23; R1441C+HDAC6 RNAi, 13; R1441C+Sirt2 RNAi, 12; right chart: N (animals)=Ctrl RNAi, 11; Y1699C, 11; Y1699C+Ctrl RNAi, 13; Y1699C+HDAC6 RNAi, 15; Y1699C+Sirt2 RNAi, 18. (c) left chart: N (animals)=Ctrl, 379; Ctrl RNAi, 326; R1441C, 367; R1441C+Ctrl RNAi, 245; R1441C+HDAC6 RNAi, 300; R1441C+Sirt2 RNAi, 218; right chart: N (animals)=Ctrl, 329; Ctrl RNAi, 281; Y1699C, 381; Y1699C+Ctrl RNAi, 338; Y1699C+HDAC6 RNAi, 413; Y1699C+Sirt2 RNAi, 170.