Coordination and interaction of the STRIPAK complex during sexual differentiation

生物体是复杂的系统，具有对交变信号做出反应的恒定能力。因此，生物体将经历主要的形态和生理变化，这些变化可以例如在分子水平上通过蛋白质复合物的动力学来识别。该项目的重点是高分子量复合物的组成部分，这些复合物在不同的信号通路之间共享，从而通过迄今为止未知的机制相互交谈。上一个资助期的一个关键发现是发现了控制模式真菌Sordaria macrospora性发育的STRIPAK蛋白复合物。该子囊菌提供了使用分子、遗传、生物化学和/或细胞生物学方法研究STRIPAK复合物的不同亚基的机会。STRIPAK的一个亚基是PRO45，一种膜相关亚基，与人肌膜相关蛋白（SLMAP）具有显著的同源性，据信SLMAP在高尔基体和中心体之间起物理和信号连接的作用，对纺锤体组装很重要。STRIPAK复合物的其他成分是蛋白磷酸酶PP 2A的三个亚基，我们将研究催化亚基PP 2Ac 1的调节功能。除此之外，我们感兴趣的是STRIPAK复合物如何与其他复合物相互作用，参与细胞信号传导。选择的蛋白质是EPS 12和NDK 1，它们最有可能与其他信号级联交叉，从而允许响应不同信号的适应。STRIPAK复合物在真核生物中高度保守，因此用真菌实验系统获得的结果将与其他真核系统具有普遍相关性。

Living organisms are complex systems that have the constant capacity to response to alternating signals. As a consequence, organisms will undergo major morphological and physiological changes that can be recognized for example at the molecular level by the dynamics of protein complexes. This project focusses on components of high molecular weight complexes that are shared between different signaling pathways and thus talk to each other through so far unknown mechanisms. A key finding of the previous funding period is the discovery of the STRIPAK protein complex, controlling sexual development in the model fungus Sordaria macrospora. This ascomycete provides the opportunity to study distinct subunits of the STRIPAK complex, using molecular, genetic, biochemical and/or cell biological approaches. One subunit of STRIPAK is PRO45, a membrane associated subunit, showing significant homology to the human Sarcolemmal membrane-associated protein (SLMAP), which is believed to serve as physical and signaling connection between the Golgi and centrosomes and is important for spindle assembly. Other components of the STRIPAK complex are three subunits of protein phosphatase PP2A, and we will investigate the modulatory function of catalytic subunit PP2Ac1. Besides that we are interested, how the STRIPAK complex interacts with other complexes, involved in cell signaling. Selected Proteins are EPS12 and NDK1, which most probably cross-talk with other signaling cascades and thus allow the adaptation in response to varying signals. The STRIPAK complex is highly conserved within eukaryotes and therefore results obtained with the fungal experimental system will be of general relevance for other eukaryotic systems.