Subcellular and intercellular trafficking of NAD+ and cyclic ADP-ribose: a new system for regulating calcium-related cell functions

Summary form only given. Regulation of levels, compartmentation and spatiotemporal dynamics of intracellular calcium is central to most functions and processes in living cells. A number of second messengers play an essential role in releasing calcium from intracellular stores in many cells, thereby regulating calcium-dependent functions. Cyclic ADP-ribose (cADPR), discovered in 1987 by H.C. Lee (Minneapolis, MN), is one of the most potent calcium mobilising metabolites. The number of known cADPR regulated cell processes via intracellular calcium release, from protists to man, is now over fifty. cADPR is generated by a family of enzymes, defined as ADP ribosyl cyclases, that convert NAD⁺ to nicotinamide and cADPR through a lyase reaction. Some of these cyclases, especially in mammalian cells, are bifunctional enzymes that, in addition to generating cADPR, can also catalyze its hydrolytic degradation to ADP-ribose (cADPR hydrolases). CD38, a 46 KDa type 11 transmembrane glycoprotein, is the best characterised among these bifunctional enzymes involved in cADPR metabolism.