Lysosome-sarcoplasmic reticulum junctions: a trigger zone for calcium signaling by nicotinic acid adenine dinucleotide phosphate and endothelin-1

Previous studies on pulmonary arterial smooth muscle cells have shown that nicotinic acid adenine dinucleotide phosphate ( NAADP) evokes highly localized intracellular Ca2+ signals by mobilizing thapsigarginin-sensitive stores. Such localized Ca2+ signals may initiate global Ca2+ waves and contraction of the myocytes through the recruitment of ryanodine receptors on the sarcoplasmic reticulum via Ca2+-induced Ca2+ release. Here we show that NAADP evokes localized Ca2+ signals by mobilizing a bafilomycin A1-sensitive, lysosome-related Ca2+ store. These lysosomal stores facilitate this process by co-localizing with a portion of the sarcoplasmic reticulum expressing ryanodine receptors to comprise a highly specialized trigger zone for NAADP-dependent Ca2+ signaling by the vasoconstrictor hormone, endothelin-1. These findings further advance our understanding of how the spatial organization of discrete, organellar Ca2+ stores may underpin the generation of differential Ca2+ signaling patterns by different Ca2+-mobilizing messengers.