title: Wash functions downstream of Rho and links linear and branched actin nucleation factors.
abstract: 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.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Liu
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Abreu-Blanco
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Barry
authors.forename: Elena V
authors.initials: EV
authors.lastname: Linardopoulou
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Osborn
authors.forename: Susan M
authors.initials: SM
authors.lastname: Parkhurst
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000378:metabolism*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009866:Oogenesis / Q000502:physiology; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins; C577014:WASH protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; C096354:capu protein, Drosophila; C402385:spir protein, Drosophila; C511153:Rho1 protein, Drosophila; D020741:rho GTP-Binding Proteins