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.
Galione
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Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK. antony.galione@pharm.ox.ac.uk
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008322:Mammals; D008954:Models, Biological; D009249:NADP / Q000031:analogs & derivatives* / Q000737:chemistry / Q000502:physiology; D015290:Second Messenger Systems; D015398:Signal Transduction
D009249:NADP; C024376:NAADP; D002118:Calcium