GMFβ prunes actin branches

Migrating fi broblasts assemble a dendritic network of branched actin fi laments that drives the formation of a lamellipodial protrusion at their leading edge. Haynes et al. reveal that, like a topiarist guiding the growth of a tree, a protein called GMF␤ " prunes " this actin network in order to guide the cell's migration towards certain directional cues (1). Branched actin networks form when nucleation-promoting factors such as WASP and SCAR/WAVE activate the Arp2/3 complex , which nucleates the assembly of new actin fi laments from the side of preexisting ones. " We know a lot about how you make actin branches, " says James Bear, from the University of North Carolina at Chapel Hill, " but we don't know much about how this network gets turned over. " Several proteins have been shown to disassemble Arp2/3-generated actin networks, including the actin-severing protein cofi lin (2). A distant relative of cofi lin, known as glia maturation factor (GMF), has also been implicated in the turnover of branched actin networks, even though this protein is unable to bind or sever actin fi laments (3, 4). Instead, experiments in vitro and in budding yeast suggest that GMF can inhibit the Arp2/3 complex's activation by nucleation-promoting factors and destabilize the com-plex's interaction with actin fi laments at network branch points (3–5). Bear and colleagues , led by graduate student Elizabeth Haynes, set out to investigate GMF's function in migrating fi bro-blasts (1). Haynes et al. first determined that GMF␤—a ubiquitously expressed isoform of the protein and the only isoform expressed in fibroblasts—transiently localized to lamellipodia generated by the Arp2/3 complex. " Fibroblasts undergo cycles of protru-sion and retraction, " explains Bear. " GMF␤ was recruited during the retraction phase when the branched actin network was being taken apart. When we knocked down GMF␤, the lamellipodia almost never retracted, and when they did, they retracted incredibly slowly. " Lamellipodia were therefore larger in GMF␤-defi cient fi broblasts, and Arp2/3-generated actin networks extended over a greater proportion of the cell perimeter. In contrast, fi broblasts overexpressing GMF␤ formed smaller, more dynamic lamellipodia than control cells. GMF␤ therefore counteracts the assembly of branched actin networks by the Arp2/3 complex. To determine whether the protein does this by destabilizing the network branch points, or by preventing Arp2/3 activation, Haynes et al. treated fi broblasts with a small molecule inhibitor of the Arp2/3 complex called CK-666. " …