Figure 2
From: Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD
Transportin-1 and arginine methylation are directly implicated in DPR models and C9 patients.
(a) Trn knockdown potently enhanced the PR-induced degenerative eye phenotype. Females are shown. (b) Computational conformational docking predictions predict that PR can fit the transportin-1 binding pocket. Positive arginine side chains of PR (red) interact with the negative side chains (blue) of the binding pocket. (c) Elav is mislocalized to the cytoplasm in PR expressing flies. Mislocalization is exacerbated upon Trn RNAi knockdown. Arrowheads indicate cytoplasmic staining. Scale bar indicates 5 μm. (d) hnRNPA3 is mislocalized in c9FTD cases (arrowheads) but not in disease-negative controls. Picture shows dentate gyrus. Scale bar indicates 10 μm. (e) Art1 knockdown enhances the PR-induced eye phenotype. Males are shown. (f) PR colocalizes with PRMT1 upon cotransfection in HeLa cells, as determined by super resolution microscopy (SIM). (g) GR staining associates with (arrowheads) and partially colocalizes with (arrow) ASYM24 staining in transfected neuroblastoma cells, as determined by SIM. Scale bars indicate 10 μm. (h) Immunostaining with ASYM24 detects methylated pathological aggregates (arrowheads) in dentate gyrus of c9FTD patient samples but not in controls. Scale bar indicates 10 μm.
