Wiskott-Aldrich Syndrome (WAS) proteins, such as Wasp and Wash, regulate branched actin networks by activating Arp2/3 in response to Rac and Cdc42 GTPases. By contrast, the linear actin nucleators Spire and Cappuccino (Capu)function downstream of Rho1 GTPase. But now, Susan Parkhurst and colleagues dzemonstrate that Rho1 and Wash regulate both linear- and branched-filament actin networks (see ). In vitro, Wash activates Arp2/3 to nucleate actin, but also bundles F-actin and microtubules (MTs). In vivo, Wash is essential for Drosophila oocyte development and functions in the Rho1/Capu/Spire pathway. It physically interacts with all three factors, the authors report,and its actin- and MT-bundling activity is regulated by both Rho1 and Spire,and intriguingly also by Arp2/3, in vivo. As Wash requires Arp2/3 to regulate the actin cytoskeleton during oogenesis, Arp2/3 might thus act as a molecular switch for Wash function. Future work should shed light on how the different actin networks are coordinated and how, when misregulated, these processes contribute to disease.
