Z-Project (coordination and central funds)

外周和中枢神经系统中的P2受体是细胞外核苷酸的靶标。尤其是ATP/ADP和UTP/UDP是重要的信号分子。我们的团队将研究神经元、神经胶质细胞及其共同前体细胞上的配体门控的P2X和G蛋白偶联的P2Y受体。我们打算阐明这些受体的结构、组装、转导途径和相互作用机制。将澄清配体结合或激动剂混杂的结构先决条件。将产生转基因小鼠，以便于相关受体类别的视觉识别和定位，以及研究它们的上调或下调及其附属蛋白。我们还将对一些选定的细胞系统(感觉神经元、星形胶质细胞、Müler细胞、小胶质细胞)进行功能研究，在这些系统中，P2X和/或P2Y受体可能在神经病理性疼痛、视网膜损伤、帕金森S病或神经退行性疾病的发展中发挥重要作用。有广泛的方法能力来实现目标。已经提到的由研究单位成员产生的转基因动物和从外部来源获得的额外的基因敲除小鼠将被集体使用。这些项目要么将在莱比锡大学医学院实施，要么将与该学院密切合作。它打算在莱比锡建立一个全国性的协调德国P2受体研究的中心。

P2 receptors in the peripheral and central nervous system are targets of extracellular nucleotides. Especially ATP/ADP and UTP/UDP are important signalling molecules. Our consortium will investigate ligand-gated P2X and G protein-coupled P2Y receptors at neurons, glial cells and their common precursor cells. We intend to elucidate the structure, assembly, transduction pathways and interaction mechanisms of these receptors. The structural pre-requisites for ligand-binding or agonist promiscuity will be clarified. Transgenic mice will be generated to facilitate the visual identification and mapping of the relevant receptor classes as well as to study their up- or down-regulation and their accessory proteins. We will also carry out functional studies on a few selected cell systems (sensory neurons, astrocytes, Müller cells, microglia) where P2X and/or P2Y receptors may play important roles in the development of e.g. neuropathic pain, retinal damage, Parkinson¿s disease or neurodegenerative illnesses. A wide methodological competence is available to approach the targeted aims. The already mentioned transgenic animals generated by the members of the Research Unit and additional knockout mice obtained from external sources will be used collectively. The projects will either be carried out at the Medical Faculty of the University of Leipzig or they will be intimately associated with this Faculty. It is intended to establish in Leipzig a nationwide center for coordinating German P2 receptor research.