Fig. 4.

Functionally linked co-pathologies emerge in response to TDP-43 acetylation-mimic aggregates. QBI-293 cells (a) or TA muscles (b) were transfected with GFP-tagged cytoplasmic localized TDP-43-ΔNLS-K145Q either alone (endogenous UBQLN-2 analysis) or in tandem with an OPTN expression plasmid for increased detection sensitivity. Either endogenous UBQLN-2 or ectopically expressed OPTN were detected by double-labeling immunofluorescence using GFP (green), UBQLN-2 (red), or OPTN (red) antibodies, while DAPI marked nuclei (blue). We note significant recruitment of both UBQLN-2 and OPTN to TDP-43 aggregates in either cell-based or muscle fiber models. White arrows highlight recruitment of UBQLN-2 or OPTN to TDP-43 aggregates. Arrowheads indicate occasional co-localization of UBQLN-2 to smaller TDP-43 pre-aggregates. Scale bar = 50 μm