NAADP, a new intracellular messenger that mobilizes Ca²⁺ from acidic stores

NAADP (nicotinic acid–adenine dinucleotide phosphate) is a recently described Ca²⁺-mobilizing molecule. First characterized in the sea urchin egg, it has been shown to mobilize Ca²⁺ from intracellular stores in a wide range of cells from different organisms. It is a remarkably potent molecule, and recent reports show that its cellular levels change in response to a variety of agonists, confirming its role as a Ca²⁺-mobilizing messenger. In many cases, NAADP appears to interact with other Ca²⁺-mobilizing messengers such as IP₃ (inositol 1,4,5-trisphosphate) and cADP-ribose in shaping cytosolic Ca²⁺ signals. What is not clear is the molecular nature of the NAADP-sensitive Ca²⁺ release mechanism and its subcellular localization. This review focuses on the recent progress made in sea urchin eggs, which indicates that NAADP activates a novel Ca²⁺ release channel distinct from the relatively well-characterized IP₃ and ryanodine receptors. Furthermore, in the sea urchin egg, the NAADP-sensitive store appears to be separate from the endoplasmic reticulum and is most likely an acidic store. These findings have also been reinforced by similar findings in mammalian cells, and a unified model for NAADP-induced Ca²⁺ signalling is presented.