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

环腺苷二磷酸核糖(CADPR)是一种钙离子动员的第二信使，主要参与T细胞的激活(Guse等人，自然398，70-73(1999))和成纤维细胞钙信号的调制器(Bruzzone等人，J.Cell Biol)。163,837-845(2003))。在本项目中，我们旨在通过使用反义或小干扰RNA方法建立兰诺定受体亚型特异性击倒T细胞和成纤维细胞克隆，并随后通过分析这些细胞中的钙信号来确定cADPR的分子靶点(S)。其次，最近发现了一种新的cADPR敏感的钙离子进入系统，将从激活机制、药理特性和电生理特性方面进行详细的分析。综上所述，该项目应该对理解T淋巴细胞和成纤维细胞中cADPR介导的钙信号转导机制做出重大贡献。

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.