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

WASH 和新型 WH2 蛋白促进 Arp2/3 介导的果蝇肌动蛋白成核的分析

• 批准号: 170417426
• 负责人: Professor Dr. Sven Bogdan
• 金额: --
• 依托单位: Arbeitsgruppe Molekulare Zellphysiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/170417426?language=en
• 关键词: Analysis; WASH; novel; WH2; protein

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.

在后生动物发育过程中，肌动蛋白聚合驱动着各种形态发生事件。控制肌动蛋白动力学的机制的紧密时空协调对于将细胞塑造成多细胞生物体的膜突起和膜运输至关重要。WASP/WAVE蛋白家族的成员是激活肌动蛋白成核复合物Arp 2/3的中心成核促进因子（NPF）。以果蝇为模型系统，我们联合收割机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Arp 2/3复合物在果蝇发育过程中如何受到不同NPF的差异调节。我们的比较，功能和生化分析两个主要的NPF，WAVE和WASP揭示了Arp 2/3依赖的肌动蛋白聚合的其他监管模式。WAVE和WASP介导的信号通路不是严格线性的，而是嵌入由不同组分组合组装形成的大分子复合物的调控网络中。其他新发现的NPF如WASH和WHAMM样蛋白如何在果蝇发育过程中调节Arp 2/3的体外和体内活性，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。