NAADP Mobilizes Ca2+ from Reserve Granules, Lysosome-Related Organelles, in Sea Urchin Eggs

Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca2+ in many cells and species. Unlike other Ca2+-mobilizing messengers, NAADP mobilizes Ca2+ from an unknown store that is not the endoplasmic reticulum, the store traditionally associated with messenger-mediated Ca2+ signaling. Here, we demonstrate the presence of a Ca2+ store in sea urchin eggs mobilized by NAADP that is dependent on a proton gradient maintained by an ATP-dependent vacuolar-type proton pump. Moreover, we provide pharmacological and biochemical evidence that this Ca2+ store is the reserve granule, the functional equivalent of a lysosome in the sea urchin egg. These findings represent an unsuspected mechanism for messenger-mediated Ca2+ release from lysosome-related organelles.