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A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation

Fig 6

Hero proteins suppress the neurotoxicity of protein aggregates in Drosophila eyes.

(A) Expression of Hero9, -13, -45, or -11 alone showed no phenotype in the external eye morphology, much as the YFP control (upper). Expression of TDP-43-YFP caused the external eye degeneration. Hero9 and double copies of Hero45 strongly suppressed the eye degeneration by TDP-43-YFP (middle and lower). (B) Knockdown of Hsc70-4 or CG17931 caused detectable external eye degeneration, compared to the mock knockdown of Piwi. (C) Nail polish imprint of eyes. Knockdown of Hsc70-4 or CG17931 caused irregular arrangements of ommatidia and bristles. (D) Knockdown of Hsc70-4 or CG17931 decreased the retinal depth. Arrowhead in the left picture indicates the retinal depth. Data represent means ± SD from 5 individual flies. (E) Knockdown Hsc70-4, CG17931, CG14818, or Vig2 caused exacerbation of the eye morphology defect by overexpression of TDP-43-YFP (upper). Knockdown of fly Hero proteins, CG17931, CG12384, or CG11444 caused exacerbation of the eye morphology defect by overexpression of aggregation-prone MJDtr-Q78 (lower). Note that female flies were used for (E), while male flies were used for (A–D). We observed the same phenotype for at least 10 flies per each genotype in each assay. The numerical data pertaining to this figure can be found in S1 Data file. Hero, heat-resistant obscure; Hsc, heat shock cognate; MJDtr-Q78, Machado-Joseph disease truncated-poly-glutamine 78; RNAi, RNA interference; YFP, yellow fluorescent protein.

Fig 6

doi: https://doi.org/10.1371/journal.pbio.3000632.g006