Figure 1.

Pbp1 is a dose-sensitive modifier of TDP-43 toxicity in yeast. a) Spotting assays with yeast TDP-43 showing toxicity. Five-fold serial dilutions of yeast cells spotted onto glucose (expression repressed) or galactose (expression induced). Upregulation of PBP1 enhances TDP-43 toxicity. Whereas PBP1 has no effect on yeast viability when expressed with the control protein YFP, when co-expressed with TDP-43, it enhances toxicity. Enhancement is specific because PBP1 does not affect the toxicity of a pathogenic Huntington fragment (htt72Q) or α–synuclein. b) Spotting assays with yeast TDP-43 showing that PBP1 deletion (pbp1Δ) suppresses TDP-43 toxicity. Whereas expression of TDP-43 from a plasmid in WT yeast was toxic, this was mitigated in pbp1Δ cells. The effect was specific because α–syn or htt72Q toxicity was not suppressed by pbp1Δ