Nicotinamide adenine dinucleotide, NAD+, is the universal currency of energy metabolism and electron transfer. Exciting results from recent studies indicate that - apart from its role as a coenzyme - NAD+ and its metabolites play important roles also in cell signalling, i.e. as substrates for nucleotide-metabolizing enzymes and by providing ligands for extra- and intracellular receptors (1-8). NAD-metabolites such as ADP-ribose, cyclic ADP-ribose, and NAADP have emerged as a key second messengers in calcium signalling (9-13). The symposium will focus on ADP-ribosyltransferases (ARTs), ADP-ribosylcyclases (ARCs), and calcium signalling. The meeting will bring together researchers from diverse fields that are engaged in the molecular characterization of the key players of NAD signalling, each of which constitutes a potential novel therapeutic target (14, 15).
Key Players in Cell-Signalling by NAD.
ADP-ribosyltransferases (ARTs), poly-ADP-ribose polymerases (PARPs), sirtuins (SIR), ADP-ribosylcylcases (ARCs) utilize the high energy bond in NAD between nicotinamide and ADP-ribose (red line). ARTs, PARPs, and SIRs transfer the ADP-ribose moiety onto acceptors (X = proteins, DNA, sugars, small molecules, water). ADP-ribosylhydrolases (ARHs) and Poly-ADP-ribose-glycohydrolases (PARGs) de-ADP-ribosylate acceptors. ARCs catalyze multiple reactions, including NAD-hydrolysis, ADPR-cyclization, and base exchange of nicotinamide by nicotinic acid, thereby generating the calcium (Ca++)-mobilizing second messengers ADP-ribose, cyclic ADP-ribose, and NAADP. NAD can act as a ligand for the P2Y11 purinoreceptor, ADPR as a ligand for the ryanodin receptor (RyR) and for proteins harboring a macro-domain. The NAD-2008 Hamburg meeting will focus on ARTs, ARCs, and calcium-mobilization (yellow highlights).
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