Cells elongate but are unable to detach their tails when the MyH9 myosin is blocked.

Try as it might to pull itself forward, an immune cell will go nowhere unless a myosin also pushes it from behind, report Morin et al. (page 195).

An immune cell holds onto the underlying matrix or another cell with the help of membrane receptors called integrins. When the cell receives a chemokine signal, the integrins change shape, allowing them to grab onto their ligands on target cells. Using the traction provided by these integrin links, the now sticky cell elongates a leading edge in the direction of migration and is trailed by a uropod—the back end of the cell.

The cell moves ahead when the integrins deactivate and the integrin-ligand bonds in the uropod are broken. The forces that unstick the uropod to allow forward propulsion are unknown.

Morin et al. hunted for these forces by looking for proteins that bind to a T cell integrin called LFA-1 in cells that are getting ready to move. They found a nonmuscle form of the myosin motor called MyH9, which is known to be required for immune cell migration. Images and videos showed that this actin-based motor docked with LFA-1 in the uropod but not in the leading edge.

Cells that were treated with a myosin inhibitor or a myosin-specific siRNA froze into comet shapes with extended uropods that failed to detach. The motor's action thus seems to break LFA-1's hold on its ligand.

Even without the myosin, the uropod integrins were already in an inactive form, as shown by their failure to bind antibodies specific for active integrins. Clusters of these inactive integrins, however, still formed weak bonds with their ligands. The positioning of the myosin near these weak attachments might allow the motor to pop them apart via actin contraction.

The mechanism that inactivates integrins in the uropod is not yet known. It is possible that integrins deactivate as they drift farther from the activating chemokine signal at the cell's leading edge.

How the myosin distinguishes between active and inactive LFA-1 is another question that still needs an answer.