The leading edge of a migrating cell is built up via one or more positive feedback loops. Kunisaki et al. (page 647) present evidence for a feedback loop that is required for the greater localization, although not greater overall abundance, of the critical migration mediator phosphatidylinositol 3,4,5-triphosphate (PIP3). The loop is driven by the newly identified Rac activator DOCK2.
Kunisaki et al. had earlier identified DOCK2 as a regulator of lymphocyte migration. They now find that DOCK2 is also required for directed migration in neutrophils. DOCK2-deficient neutrophils migrated at almost half the speed of wild-type cells, and wandered rather than taking a straight path toward a chemoattractant. The leading edge in these cells was not as stable as that found in wild-type neutrophils.
In the presence of chemoattractant, DOCK2 translocated to the neutrophil leading edge in a PI3K-dependent manner. Its presence there...
