Figure 6. Geranylgeranylation of small GTPases is critical for endothelial junction integrity.

(A) HUVECs were treated with 100 µM GGTI overnight, and cytosolic and membrane protein fractions isolated. (B) HUVECs in transwell experiments were treated with 100 µM GGTI or 100 µM FTI overnight, followed by 1 U/ml thrombin challenge. Monolayer permeability is determined by FITC-dextran fluorescent density in the bottom chamber medium. Data are expressed as means ± S.E. (n = 4 samples per group), * p<0.05. (C) HUVECs seeded on glass slides were treated with GGTI or FTI, followed by thrombin challenge as indicated. Slides were stained with VE-cadherin primary antibody and Texas Red-conjugated secondary antibody, and then visualized by fluorescence microscopy as described in Methods. The white arrows indicate gaps between endothelial cells.