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

在后生动物发育过程中，肌动蛋白聚合驱动多种形态发生事件。控制肌动蛋白动力学机制的紧密时空协调对于将细胞塑造成多细胞生物的膜突出和膜运输至关重要。WASP/WAVE蛋白家族的成员是激活肌动蛋白成核复合体Arp2/3的中心成核促进因子（NPF）。以果蝇为模型系统，我们将强大的遗传工具与生物化学和细胞生物学方法相结合，剖析了在果蝇发育过程中不同npf如何对Arp2/3复合物进行差异调节。我们对两个主要的npf， WAVE和WASP进行了比较、功能和生化分析，揭示了arp2 /3依赖性肌动蛋白聚合的其他调节模式。WAVE和wasp介导的信号通路不是严格线性的，而是嵌入在由不同组分组合组装形成的大分子复合物的调节网络中。在果蝇发育过程中，其他新发现的npf如WASH和wham样蛋白如何在体外和体内调节Arp2/3活性，以及它们如何参与这些信号网络是我们未来研究的主要目标。

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.