Extended Data Fig. 8: Recruitment to the PML NB core component Sp100 protects TDP-43 from stress-induced aggregation.
From: Induced proximity to PML protects TDP-43 from aggregation via SUMO–ubiquitin networks
a, HeLa cells were genetically engineered to express RNF4-3×Flag from the endogenous RNF4 locus. Cells were transfected with FRB–Sp100–Myc and HA–TDP-43–FKBP for 24 h and either mock-treated or treated with rapamycin (100 nM, 3 h). Inset areas are indicated with yellow squares. Scale bar, 5 µm. b, Statistical analysis of the images shown in a. Enrichment of HA–TDP-43–FKBP in FRB–Sp100–Myc-positive nuclear bodies (leftmost plot) and the correlation of the indicated signal pairs within the nucleus were analyzed. At least 55 cells per condition were measured. The p values of two-tailed, unpaired Student’s t-tests are indicated. c, Statistical analysis of HA–TDP-43–FKBP insolubility in HEK293T cells transfected with HA–TDP-43–FKBP and FRB–Sp100–Myc. The insoluble fraction of HA–TDP-43–FKBP (in % of total HA–TDP-43–FKBP) was determined in solubility assays, as shown in Fig. 5i. P values of two-tailed, unpaired Student’s t-tests are indicated; error bars show the standard deviation of the mean (n = 3).
