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，因为它的错误折叠构象是人类和动物神经退行性疾病（如BSE）的病原体-但其生理功能知之甚少。我们在斑马鱼和细胞中的工作表明PrP在细胞-细胞通信/粘附和与钙粘蛋白粘附系统的相互作用中的作用。此外，我们的研究结果表明，与微结构域支架蛋白雷吉（flotillin）及其信号合作伙伴的PrP的信号转导。基于这些发现，我们提出了一个假设，即聚集在reggie微区允许PrP将信号传递到细胞中，并与肌动蛋白细胞骨架通讯。在这里，我们的目的是了解PrP的贡献，细胞间接触的形成与雷吉及其联营公司和招聘的钙粘蛋白形成接触。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，p120 ctn，Rho-GTPases等的贡献细胞接触形成，调节肌动蛋白细胞骨架和神经突生长。我们的分析将包括确定PrP-reggie在丝状伪足和片状伪足中的功能，这些伪足和片状伪足建立了细胞之间的第一次接触，并可能招募p120和钙粘蛋白用于细胞接触成熟。

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.