Anthrax ET activates Rac1 and RTK signaling to induce F-actin reorganization and endothelial permeability , Jain et al, 2025
Description
Anthrax Edema Toxin induces F-actin reorganization and edema in human Brain endothelial cells (HBMECs) in mouse footpads. Figure 1A: raw confocal images of F-actin stains (Phalloidin 488) of HBMECs used for the analyses presented in Figure 1B. Figure 1B: This data presents quantifications of F-actin fibers in untreated cells (UT), and in cells treated with ET, a mutant form of ET (ETmut) that cannot produce cAMP, and PA, the receptor-binding component of ET (ET = EF +PA). We find that ET causes a strong loss of actin stress fibers. Interestingly, ETmut and PA also induce a loss of actin stress fibers, but this phenotype is much weaker than for ET, indicating that cAMP production by EF is the main factor triggering F-actin reorganization, but that cAMP-independent effects are also at play. Figure 2C-Phalloidin: F-actin Phalloidin stains, showing Untreated HBMECs, cells treated cells with the Rac1 inhibitor NSC23766, ET-treated cells, and ET-treated cells with the Rac1 inhibitor NSC23766. Figure 2C: quantitative analysis of phalloidin stains. Rac1 inhibitor NSC23766 alleviates F-actin fiber loss by ET, indicating that Rac1 mediates ET effects on F-actin. Figure 6B-C: MEK inhibitor AS-703026, PI3K inhibitor GDC-0941 and Rac1 inhibitor NSC23766, prevent ET-induced foot pad edema in mice.