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Figure 10
ALS-Linked PDI Mutants (D292N and R300H) Are Not Protective against Mutant TDP-43 and Mutant SOD1
(A) Cells expressing TDP-M337V with empty vector alone (row 1) or co-expressing PDI-WT, PDI-D292N or PDI-R300H (rows 2, 3, 4).
(B) Significantly fewer cells formed inclusions when PDI-WT was co-expressed with TDP-M337V (∗p < 0.05) compared with PDI-D292N and PDI-R300H (∗p < 0.05).
(C) Cells expressing EGFP-tagged TDP-M337V (row 1), or co-expressing PDI-WT, PDI-D292N or PDI-R300H (rows 2, 3, 4).
(D) Co-expression of PDI-WT (∗p < 0.05) with mutant TDP-M337V significantly reduced the proportion of cells with cytoplasmic TDP-43 expression compared with those co-expressing PDI-D292N or PDI-R300H (∗p < 0.05).
(E) Cells expressing SOD1-A4V (row 1) or co-expressing PDI-WT, PDI-D292N or PDI-R300H (rows 2, 3, 4).
(F) Significantly fewer cells with inclusions were observed when PDI-WT was co-expressed with SOD1-A4V (∗p < 0.05) compared with either PDI D292N (∗∗p < 0.01) or PDI R300H (∗p < 0.01).
(G) Neuro-2a cells expressing SOD1-A4V (row 1) or co-expressing PDI-WT, PDI-D292N or PDI-R300H (rows 2, 3, 4).
(H) Over-expression of PDI-WT (∗∗p < 0.01) with SOD1-A4V resulted in significantly fewer cells with apoptotic nuclei compared with those expressing empty vector and those co-expressing PDI-D292N or PDI-R300H (∗p < 0.05).
Scale bars: 6 μm in (A), (C), (E), and (G).