Analysis of Enabled (Ena) and GUK-holder (GUKh) in regulating WAVE-driven actin dynamics in Drosophila

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The actin cytoskeleton provides mechanical forces to drive cell shape changes and cell migration during morphogenesis. Actin polymerization is controlled by members of the WASP/WAVE protein family that activate the actin nucleating complex Arp2/3. WASP and WAVE exist in multi-protein complexes regulating distinct aspects of Arp2/3 function in Drosophila development. Our recent structure-function analyses revealed an intricate interplay between members of the WAVE complex and different actin accessory proteins. We have found that the central subunit of the WAVE complex, Abi binds directly to the EVH1 domain of the actin elongator Enabled (Ena) in Drosophila. This interaction is crucial for WAVE complex function in vivo. How does Ena regulate WAVE activity in vivo? We will continue our molecular analysis of the role of Ena in regulating WAVE function during Drosophila development. In addition, we started a genetic and biochemical analysis of GUK-holder (GUKh), a conserved WAVE homology domain containing protein. Co-immunoprecipitation experiments demonstrate an interaction between GUKh and members of the WAVE complex. Live-imaging studies revealed that GUKh exhibit microtubule plus end tracking ability and recruits Abi to microtubules. The goal of our future studies is to understand how GUKh acts on WAVE function and how GUKh might integrate actin and microtubule dynamics in vivo.