Roles of the GPI-anchored proteins PrP and Thy-1 in axon growth and regeneration

GPI 锚定蛋白 PrP 和 Thy-1 在轴突生长和再生中的作用

• 批准号: 171109318
• 负责人: Professorin Dr. Claudia Stürmer
• 金额: --
• 依托单位: Arbeitsgruppe Neurobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/171109318?language=en
• 关键词: Roles; GPI; anchored; proteins; PrP

In contrast to mammals, retinal ganglion cell (RGC) axons in fish regenerate successfully after optic nerve lesion. Recent own evidence suggests that the ability of fish RGCs to upregulate growth-associated molecules, such as the microdomain-forming reggie proteins, is causally linked to successful regeneration. Our recent results show that the GPI-anchored prion proteins, fish PrP-1 and PrP-2 (PrPc in mammals), as well as Thy-1 also represent growth-associated proteins. Interestingly, PrP and Thy-1 cocluster in reggie microdomains and communicate with associated signal transduction molecules and regulate Rho-GTPases and actin dynamics. In this proposal, 1.) the contribution of PrP and Thy-1 to axon regeneration in vivo and to axogenesis and process formation in single cells in vitro will be analysed using morpholino and siRNA-mediated knockdown and protein overexpression. 2.) Furthermore, signalling molecules which communicate with PrP and Thy-1 – through their association with the reggies - and how they regulate Rho-GTPases and actin dynamics will be determined, and 3.) whether and how they promote the recruitment of specific membrane proteins, process extension and axon growth. This work aims at elucidating molecular mechanisms underlying axon regeneration and at providing new insights into the function(s) of PrP and Thy-1 which are well known but their role has remained elusive.

与哺乳动物相比，鱼类的视网膜神经节细胞 (RGC) 轴突在视神经损伤后能够成功再生，最近的证据表明，鱼类 RGC 上调生长相关分子（例如形成微域的雷吉蛋白）的能力之间存在因果关系。我们最近的结果表明，GPI 锚定的朊病毒蛋白、鱼类 PrP-1 和 PrP-2（哺乳动物中的 PrPc）以及Thy-1 还代表生长相关蛋白，PrP 和 Thy-1 共聚在 reggie 微域中，并与相关信号转导分子进行通信并调节 Rho-GTP 酶和肌动蛋白动力学。在该提议中，1.) PrP 和 Thy 的贡献。 -1 对体内轴突再生以及体外单细胞中轴突形成和过程形成的影响将使用吗啉代和 siRNA 介导的敲低和蛋白质过表达进行分析。 2.) 此外，将确定与 PrP 和 Thy-1 通信的信号分子（通过它们与 reggies 的关联）以及它们如何调节 Rho-GTP 酶和肌动蛋白动力学，以及 3.) 它们是否以及如何促进特定的招募这项工作旨在阐明轴突再生的分子机制，并为 PrP 和 Thy-1 的功能提供新的见解，这些功能众所周知，但它们的作用仍然存在。难以捉摸。