van Buul et al. show, the GTPase RhoG helps the cells make the crossing.
As leukocytes exit a blood vessel, they either pass right through the endothelial cells in the lining or wriggle between them. To get across this layer, a leukocyte first hooks onto the protruding protein ICAM1. An endothelial cell then puckers its membrane to produce a cup that cradles the leukocyte. The molecular events that prompt cup formation remain unclear. The endothelial structures resemble the phagocytic cups that allow cells to gobble pathogens. Because the GTPase RhoG spurs phagocytosis in certain cells, van Buul et al. wanted to determine whether the molecule also promotes construction of endothelial cups.
The researchers found that the binding of a leukocyte to ICAM1 activated RhoG, which congregated at the site of attachment. Knocking down RhoG with RNAi slashed the number of cups that cells fashioned and the number of leukocytes making the crossing.
An activator of RhoG, called SGEF, bound to the cytoplasmic side of ICAM1, suggesting that the molecule might link ICAM1 engagement to RhoG activation. Supporting that hypothesis, RNAi against SGEF decreased cup formation and hindered leukocyte crossing. Still unresolved is how the cups allow a leukocyte to slip through the endothelium.