Without Endo180 to release their tails, cells elongate instead of migrating.

Like jilted lovers, migrating cells need to let go before they can move on. Slithering cells get help from endosomes, via a receptor that spurs tails to detach from the surface, as Sturge et al. show on page 337.

Before it travels, a cell breaks down the focal adhesions that link it to a substrate or the adherens junctions that bind it to other cells. Activation of Rho kinase (ROCK) aids the process by enabling the cell to disengage its rear end, but what controls ROCK isn't certain. Sturge et al. investigated the possible role of endosomes, which get involved in a multitude of cell signaling events. They find that an endosome-localized receptor, called Endo180, triggers migration by breaking connections.

Internalized Endo180 is known to set off migration. The authors found that, when cancer cells were depleted of Endo180, their front ends advanced, but their tails remained anchored, and they stretched like pieces of taffy. The loss of two other endosome receptors, however, did not interfere with crawling.

Endo180 also disrupted adherens junctions. Cranking up production of the protein cut the amount of E-cadherin at these contact points, destabilizing the connections between cells.

To determine whether Endo180 works by activating ROCK, the researchers measured phosphorylation of myosin light chain-2, which retracts the cell's tail. ROCK adds phosphate groups to the myosin, but the degree of phosphorylation plunged in the Endo180-depleted cells. Just how the receptor activates ROCK has not been worked out.

Endo180 cycles between endosomes and the cell surface, and the study's findings suggest that it is the internal version that frees the tail. Endosomes sporting Endo180 accumulate in the rear of cells. And cells expressing a version of Endo180 that remains at the plasma membrane failed to detach. Extracellular collagen, Endo180's favorite ligand, was not necessary for deadhesion, but it is possible that collagen produced within motile cells might promote or limit its signaling capacity.