Funktionen des zellulären Prion Proteins für die Entwicklung von Zell-Zell Kontakten und Axonwachstum

gpi锚定的朊蛋白（PrP）是众所周知的，因为它的错误折叠的构象是人类和动物的神经退行性疾病（如疯牛病）的病原体，但它的生理功能知之甚少。我们在斑马鱼和细胞中的研究表明，PrP在细胞间通讯/粘附以及与钙粘蛋白粘附系统的相互作用中发挥了作用。此外，我们的研究结果表明，PrP与微结构域支架蛋白reggie （flotillin）及其信号伙伴相关。基于这些发现，我们提出了一种假设，即聚类在reggie微结构域允许PrP将信号转导到细胞中并与肌动蛋白细胞骨架进行通信。在这里，我们的目的是了解PrP对细胞-细胞接触形成的贡献，结合reggie及其相关物，以及钙粘蛋白的招募来形成接触。这两个事件都需要肌动蛋白细胞骨架重组。因此，我们将分析特定的适配器和信号转导分子，如CAP， afadin， src酪氨酸激酶，p120ctn， Rho-GTPases等，对细胞接触形成，肌动蛋白细胞骨架和神经突生长的调节的贡献。我们的分析将包括确定丝状足和板足中的PrP-reggie功能，它们在细胞之间建立第一次接触，并可能招募p120和钙粘蛋白来促进细胞接触成熟。

The GPI-anchored Prion protein (PrP) is well-known since its misfolded conformer is the causative agent of the neurodegenerative diseases in man and animals (such as BSE) - but its physiological function is poorly understood. Our work in zebrafish and cells suggests a role of PrP in cell-cell communication/adhesion and interaction with the cadherin adhesion system. Our results, moreover, show signal transduction by PrP in association with the microdomain scaffolding protein reggie (flotillin) and its signalling partners. Based on these findings we developed the hypothesis that clustering in reggie microdomains allows PrP to transduce signals into the cell and to communicate with the actin cytoskeleton. Here, we aim at understanding the contribution of PrP to cell-cell contact formation in conjunction with reggie and its associates and to the recruitment of cadherins to forming contacts. Both events require actin cytoskeletal reorganisation. We will therefore analyse the contribution of specific adapter and signal transduction molecules such as CAP, afadin, src tyrosine kinases, p120ctn, Rho-GTPases etc. to cell contact formation, regulation of the actin cytoskeleton and neurite growth. Our analysis will include determination of PrP-reggie function in filopodia and lamellipodia which establish first contacts between cells and which may recruit p120 and cadherins for cell contact maturation.