Molekulare Wirkorte des Calcium-mobilisierenden Second Messengers cyclic ADP-ribose in T-Lymphocyten und Fibroblasten

环腺苷二磷酸核糖（cADPR）是基本上参与T细胞活化的Ca2+动员第二信使（Guse等人，Nature 398，70 - 73（1999））和成纤维细胞Ca2+信号传导的调节剂（Bruzzone等人，163，837 - 845（2003））。在这个项目中，我们的目标是通过建立兰尼碱受体亚型特异性敲低的T细胞和成纤维细胞克隆，使用反义或siRNA的方法，并随后通过分析这些细胞中的Ca2+信号转导来确定cADPR的分子靶点。其次，最近发现了一种新的cADPR敏感的Ca 2+内流系统，将详细分析其激活机制、药理学特征和电生理学特性。总之，该项目应有助于显着的cADPR介导的Ca2+信号在T淋巴细胞和成纤维细胞的机制的理解。

Cyclic adenosine diphosphoribose (cADPR) is a Ca2+-mobilizing second messenger essentially involved in T cell activation (Guse et al., Nature 398, 70-73 (1999)) and a modulator of fibroblast Ca2+ signalling (Bruzzone et al., J. Cell Biol. 163, 837-845 (2003)). In this project we aim to identify the molecular target(s) for cADPR by establishing ryanodine receptor subtype specific knock-down T cell and fibroblast clones using either antisense or siRNA approaches, and subsequently by alalysing Ca2+ signalling in those cells. Secondly, a novel, cADPR-sensitive Ca2+ entry system has been discovered recently which will be analysed in detail regarding activation mechanism, pharmacological profile and electrophysiological properties. In summary, the project should contribute significantly to the unterstanding of the mechanisms underlying cADPR-mediated Ca2+ signalling in both T-lymphocytes and fibroblasts.