Analysis of WASH and a novel WH2 protein in promoting Arp2/3-mediated actin nucleation in Drosophila

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Actin polymerization drives a variety of morphogenetic events during metazoan development. A tight spatio-temporal coordination of the machineries controlling actin dynamics is crucial for membrane protrusion and membrane trafficking that shape cells into a multicellular organism. Members of the WASP/WAVE protein family are central nucleation-promoting factors (NPF) that activate the actin nucleating complex Arp2/3. Using Drosophila as a model system we combine the powerful genetic tools with biochemical and cell-biological methods to dissect how the Arp2/3 complex is differentially regulated by different NPFs during Drosophila development. Our comparative, functional and biochemical analysis of two main NPFs, WAVE and WASP revealed additional regulatory modes of Arp2/3-dependent actin polymerization. WAVE- and WASP-mediated signaling pathways are not strictly linear but embedded within regulatory networks of macromolecular complexes formed by the combinatorial assembly of different components. How additional new identified NPFs such as WASH and a WHAMM-like protein regulate Arp2/3 activity in vitro and in vivo during Drosophila development and and how they participate in these signaling networks is a major goal of our future studies.