Cells without RhoA activity can't pick up their tails.

In fibroblasts, the small GTPase RhoA is required for the formation of integrin-containing adhesions. Surprisingly, Worthylake et al. (page 147) have found that RhoA serves a different purpose in monocytes, apparently operating as a negative regulator of integrin adhesions at the rear of migrating cells. The authors used a tissue culture system that mimics the transendothelial migration of monocytes from blood vessels into adjacent tissues, a model which is relevant to immune system function and tumor metastasis.

When RhoA activity is inhibited in monocytes in this system, the cells attach to the endothelium, crawl forward, and begin to invade between endothelial cells. But the inhibited cells are unable to retract their tails to complete the migration. The RhoA effector p160ROCK is necessary and sufficient to allow tail retraction, and signaling through p160ROCK negatively regulates integrin adhesions. In monocytes, RhoA signaling therefore appears to couple rear retraction with forward movement in order to allow transendothelial migration. If this model is correct, RhoA activity might be localized to the rear of the migrating monocytes, a prediction the authors hope to test in the near future. ▪