Liu Raymond, Abreu-Blanco Maria Teresa, Barry Kevin C, Linardopoulou Elena V, Osborn Gregory E, Parkhurst Susan M
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Development. 2009 Aug;136(16):2849-60. doi: 10.1242/dev.035246.
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.
威斯科特-奥尔德里奇综合征（WAS）家族蛋白是Arp2/3激活剂，可介导细胞骨架重塑、细胞内运输和细胞运动所需的分支肌动蛋白网络形成。该家族的两个创始成员Wasp和Scar/WAVE分别受小GTP酶Cdc42和Rac调节。相比之下，线性肌动蛋白成核剂，如Spire和formin，受小GTP酶Rho调节。我们最近鉴定出第三个WAS家族成员，称为Wash，具有Arp2/3介导的肌动蛋白成核活性。我们发现果蝇Wash在遗传上与Arp2/3相互作用，并且在果蝇卵子发生过程中，在Rho1下游与Spire和formin Cappuccino一起发挥作用，以控制肌动蛋白和微管动力学。Wash使F-肌动蛋白束集并交联微管，受Rho1、Spire和Arp2/3调节，并且对于卵室中的肌动蛋白细胞骨架组织至关重要。我们的结果确立了Wash和Rho作为线性和分支肌动蛋白网络的调节因子，并提出了一种Arp2/3介导的机制，说明细胞如何协调调节这些结构。
