(A) Immunofluorescence for TREX1 and Calreticulin in the indicated cells. Arrows denote intact or ruptured MN. (B) Quantification of TREX1 and Calreticulin signal intensity at MN (Pearson r = 0.72 HeLa; r = 0.59 MCF10A). (C) Live-cell imaging of HeLa cells expressing GFP-TREX1, RFP-KDEL, and NLS-3×mTurquoise2. Arrow marks MN. (D) Quantification of the relative fluorescence signal intensities of GFP-TREX1, RFP-KDEL, and NLS-3×mTurquoise2 at MN (t = 0 MNE rupture) as shown in (C). Relative mean fluorescence intensities and s.d. are shown (n = 19 MN imaged in cells expressing NLS-3×mTurquoise2, GFP-TREX1, RFP-KDEL). (E) Live-cell imaging of HeLa cells expressing GFP-TREX1 and NLS-3×mTurquoise2. (F) Quantification of the relative fluorescence signal intensities of GFP-TREX1, ER tracker dye, and NLS-3×mTurquoise2. (t = 0 MNE rupture) as shown in (E). Relative mean fluorescence intensities and s.d. are shown (n = 28 MN imaged in cells expressing NLS-3×mTurquoise2, GFP-TREX1, and stained with ER tracker). (G) Schematic of full length TREX1, TREX1ΔC, and TREXΔC-Sec61-TMD. (H,I) Immunofluorescence for GFP (TREX1) and (H) Calreticulin or (I) LSD1 in the indicated cell lines. Arrows mark ruptured MN. (J) Quantification of the percentage of GFP-TREX1-positive ruptured and intact MN as shown in (E). Mean and s.d. of n = 3 experiments are shown (>180 MN quantified per replicate and cell line). P values were calculated by one-way ANOVA with Tukey’s multiple comparisons test (****P < 0.0001). All scale bars = 10 μm.