Modular proteins as organizers in the actin cytoskeleton: Integrators of functions

模块化蛋白质的使用允许这些成分参与许多不同的细胞反应。在细胞骨架蛋白中定义的模块包括PH、SH3、PDZ和WD40结构域。含有这些基序的蛋白质构成了分子复合物的基础，这些分子复合物组织细胞信号并将成分组装成功能单元。在这里，我们主要研究含有WD40结构域的冠蛋白家族。哺乳动物和盘状网柱体短冠蛋白通常是肌动蛋白细胞骨架的重要调节因子，影响细胞迁移、内吞和吞噬以及细胞分裂，而单个酵母短冠蛋白CRNll还与微管相互作用。除此之外，一些冠状蛋白，特别是CRN7亚家族的长冠状蛋白，已被证明参与囊泡运输。本研究的目的是利用哺乳动物短链CRN2和长链CRN7以及盘状盘齿龙CRN7分析冠状蛋白的分子机制、与细胞组分的相互作用、活性调控以及阐明冠状蛋白在体内的作用。

The use of modular proteins allows the involvement of these components in many different cellular reactions. The modules that have been defined in cytoskeletal proteins involve PH, SH3, PDZ and WD40 domains. Proteins containing such motifs form the basis of molecular complexes that organize cellular signalling and assemble components into functional units. Here, we concentrate on the coronin family of WD40 domain containing proteins. Mammalian and Dictyostelium discoideum short coronin proteins generally are important regulators of the actin cytoskeleton and influence cell migration, endocytosis and phagocytosis, and cytokinesis, while the single short yeast coronin CRNll additionally interacts with microtubules. Apart from that several coronins, particularly long coronins of the CRN7 subfamily, have been shown to participate in vesicular transport. Goal of the proposed studies is the analysis of the molecular mechanisms, interactions with cellular components, regulation of activity, and elucidation of the in vivo roles of coronin proteins using the mammalian short CRN2 and long CRN7 as well as Dictyostelium discoideum CRN7.