Subcellular and intercellular trafficking of NAD{sup}+ and Cyclic ADP-ribose: A new system for regulating calcium-related cell functions.

摘要

Regulation of levels, compartmentation and spatio-temporal 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{sup}+ to nicotinamide and cADPR through a lyase reaction. Some of these cyclases, especially in mammalian cells, are bifunctional enzymes that, in addition to generathg cADPR, can also catalyze its hydrolytic degradation to ADP-ribose (cADPR hydrolases). CD38, a 46 KDa type II transmembrane glycoprotein, is the best characterised among these bifunctional enzymes involved in cADPR metabolism.