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Novel WRC interacting receptors transducing signals at the membrane to the actin cytoskeleton

新型 WRC 相互作用受体将膜上的信号转导至肌动蛋白细胞骨架

基本信息

批准号：
316970849
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：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/316970849?language=en
关键词：
Novel WRC interacting receptors transducing

项目摘要

Cell shape changes require a dynamic interplay between membrane remodeling and the actin cytoskeleton by which environmental signals are translated into changes in morphol-ogy and motility. The WASP family verprolin homologous (WAVE) protein is a key activator of the Arp2/3 complex and coordinates actin nucleation in many cellular processes including adhesion, migration and phagocytosis. The WAVE protein is constitutively incor-porated into a conserved, heteropentameric complex, the WAVE regulatory complex (WRC) that controls its activity in time and space. We recently described a novel mecha-nism by which the WRC can directly be recruited to membranes through a conserved pep-tide motif (WIRS) found in a variety of transmembrane and membrane-associated proteins. This provides a new signaling platform by which environmental signals might be translated into changes in morphology and motility. Here, we will analyze collective follicle cell migration in Drosophila oogenesis and wound-induced directed single cell migration of Drosophila immune cells and dissect how these WIRS surface receptors bridge ligands to changes of the actin cytoskeleton.

细胞形态的改变需要细胞膜重塑和肌动蛋白细胞骨架之间的动态相互作用，环境信号通过肌动蛋白细胞骨架转化为形态学和运动性的变化。WASP家族verprolin同源（WAVE）蛋白是Arp 2/3复合物的关键激活剂，并在许多细胞过程（包括粘附、迁移和吞噬）中协调肌动蛋白成核。WAVE蛋白组成性地整合到一个保守的异五聚体复合物中，即WAVE调节复合物（WRC），该复合物控制其在时间和空间上的活性。我们最近描述了一种新的机制，通过这种机制，WRC可以通过在各种跨膜和膜相关蛋白中发现的保守肽基序（WIRS）直接被募集到膜上。这提供了一个新的信号平台，通过该平台，环境信号可能被转化为形态和运动的变化。在这里，我们将分析集体卵泡细胞迁移在果蝇卵子发生和伤口诱导的果蝇免疫细胞的定向单细胞迁移和解剖这些WIRS表面受体如何桥接配体的肌动蛋白细胞骨架的变化。