Ena orchestrates remodelling within the actin cytoskeleton to drive robust Drosophila macrophage chemotaxis.

The actin cytoskeleton is the engine that powers the inflammatory chemotaxis of immune cells to sites of tissue damage or infection. Here we combine genetics with live, in vivo imaging to investigate how cytoskeletal rearrangements drive macrophage recruitment to wounds in Drosophila We find that the actin-regulatory protein Ena is a master regulator of lamellipodial dynamics in migrating macrophages where it remodels the cytoskeleton to form linear filaments that can then be bundled together by the cross-linker Fascin. In contrast, the formin Dia generates rare, probing filopods for specialised functions that are not required for migration.Ena's role in lamellipodial bundling is so fundamental that its over-expression increases bundling even in the absence of Fascin by marshalling the remaining cross-linking proteins to compensate. This reorganisation of the lamellipod generates cytoskeletal struts that push against the membrane to drive leading edge advancement and boost cell speed. Thus, Ena-mediated remodeling extracts the most from the cytoskeleton to power robust macrophage chemotaxis during their inflammatory recruitment to wounds.