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.