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Ca2+动员的第二信使，主要参与T细胞活化（Guse等人，Nature 398, 70-73(1999)）和成纤维细胞Ca2+信号的调节剂（Bruzzone等人，J. cell Biol. 163, 837-845(2003)）。在这个项目中，我们的目标是通过使用反义或siRNA方法建立ryanodine受体亚型特异性敲除T细胞和成纤维细胞克隆，并随后通过分析这些细胞中的Ca2+信号传导来鉴定cADPR的分子靶标。其次，最近发现了一种新的，cadpr敏感的Ca2+进入系统，将详细分析其激活机制，药理特征和电生理特性。总之，该项目应该有助于理解cadpr介导的t淋巴细胞和成纤维细胞中Ca2+信号传导的机制。

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.