PI3K (red) is recruited (left to right) to membrane rafts (green) at the leading edge.

The plasma membrane polarizes in moving cells by reorganizing lipid rafts, according to Gómez-Moutón et al. on page 759. This polarization puts migration tools at the correct end of the cell.

The polarization of signaling molecules such as PI3K allows migrating cells to respond directionally to chemotactic signals by forming lamellipodia at the front and uropods at the rear. Gómez-Moutón et al. show that this localized signaling is a result of redistribution of plasma membrane lipid compartments that puts chemokine receptors at the front of cells. Using live migrating white blood cells, the group watched in real time as some rafts moved to the cell's leading edge, while other rafts moved to the rear.

Rafts that moved to the front contained the CCR5 chemotactic receptor. Wherever CCR5 was found, the authors also saw activated PI3K—a key determinant in the orientation of migration. Disruption of raft polarization, by removing cholesterol, prevented this localized PI3K recruitment and thus stopped directed migration.

So far it is unclear how different rafts choose between the front and rear of the cell. Perhaps activation of a few receptors on one side of the cell initiates the clustering of several receptor- containing rafts. As the actin cytoskeleton is needed for raft polarization, the authors speculate that the PI3K brought to these rafts may activate proteins that alter actin dynamics to recruit more of the appropriate rafts. One of these proteins could be the GTPase Rac1, whose activation at the leading edge is required for cell migration. Rac1 was recently shown to bind to and be activated specifically at lipid rafts (del Pozo, M.A., et al. 2004. Science. 303:839–842).

Other proteins in different rafts might initiate raft movement to the rear. Further insight awaits the characterization of the lipid and protein components of the different rafts. ▪