Fig. 4.

Dissecting the molecular determinants of TDP-43 aggregation and toxicity. (A) A diagram illustrating the domain structure of TDP-43 along with various truncation constructs used in this study (a–l). (B) Structure/function analysis testing the effects of truncations on TDP-43-GFP localization by fluorescence microscopy and toxicity by spotting assays (C). The C-terminal region is required for aggregation and toxicity (compare constructs a and d), but by itself is not sufficient (construct j). A construct harboring the C-terminal region along with RRM2 recapitulates the complete aggregation and toxicity of full-length TDP-43 (construct g). RRM, RNA recognition motif; C-term, C-terminal region; NLS, nuclear localization signal.