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Wash functions downstream of Rho and links linear and branched actin nucleation factors

TitleWash functions downstream of Rho and links linear and branched actin nucleation factors
Publication TypeJournal Article
Year of Publication2009
AuthorsLiu R, Abreu-Blanco MT, Barry KC, Linardopoulou EV, Osborn GE, Parkhurst SM
Date Published2009
ISBN Number1477-9129 (Electronic)0950-1991 (Linking)
KeywordsActin-Related Protein 2-3 Complex/genetics/metabolism, Actins/genetics/*metabolism, Animals, Cytoskeleton/metabolism, Drosophila melanogaster/anatomy & histology/*metabolism, Drosophila Proteins/genetics/*metabolism, Female, Monoterpenes, Mice, Inbred BALB C, Microfilament Proteins/genetics/*metabolism, Microtubules/metabolism, Oogenesis/physiology, Ovary/cytology/metabolism, rho GTP-Binding Proteins/genetics/*metabolism, Wiskott-Aldrich Syndrome Protein/genetics/*metabolism

Wiskott-Aldrich Syndrome (WAS) family proteins are Arp2/3 activators that mediate the branched-actin network formation required for cytoskeletal remodeling, intracellular transport and cell locomotion. Wasp and Scar/WAVE, the two founding members of the family, are regulated by the GTPases Cdc42 and Rac, respectively. By contrast, linear actin nucleators, such as Spire and formins, are regulated by the GTPase Rho. We recently identified a third WAS family member, called Wash, with Arp2/3-mediated actin nucleation activity. We show that Drosophila Wash interacts genetically with Arp2/3, and also functions downstream of Rho1 with Spire and the formin Cappuccino to control actin and microtubule dynamics during Drosophila oogenesis. Wash bundles and crosslinks F-actin and microtubules, is regulated by Rho1, Spire and Arp2/3, and is essential for actin cytoskeleton organization in the egg chamber. Our results establish Wash and Rho as regulators of both linear- and branched-actin networks, and suggest an Arp2/3-mediated mechanism for how cells might coordinately regulate these structures.