A primer of NAADP-mediated Ca(2+) signalling: From sea urchin eggs to mammalian cells

Since the discovery of the Ca(2+) mobilizing effects of the pyridine nucleotide metabolite, nicotinic acid adenine dinucleotide phosphate (NAADP), this molecule has been demonstrated to function as a Ca(2+) mobilizing intracellular messenger in a wide range of cell types. In this review, I will briefly summarize the distinct principles behind NAADP-mediated Ca(2+) signalling before going on to outline the role of this messenger in the physiology of specific cell types. Central to the discussion here is the finding that NAADP principally mobilizes Ca(2+) from acidic organelles such as lysosomes and it is this property that allows NAADP to play a unique role in intracellular Ca(2+) signalling. Lysosomes and related organelles are small Ca(2+) stores but importantly may also initiate a two-way dialogue with other Ca(2+) storage organelles to amplify Ca(2+) release, and may be strategically localized to influence localized Ca(2+) signalling microdomains. The study of NAADP signalling has created a new and fruitful focus on the lysosome and endolysosomal system as major players in calcium signalling and pathophysiology.