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

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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.