부산대학교 도서관

Lysosomes and the endoplasmic reticulum (ER) are Ca2+stores mobilized by the second messengers NAADP and IP3, respectively. Here, we establish Ca2+signals between the two sources as fundamental building blocks that couple local release to global changes in Ca2+. Cell-wide Ca2+signals evoked by activation of endogenous NAADP-sensitive channels on lysosomes comprise both local and global components and exhibit a major dependence on ER Ca2+despite their lysosomal origin. Knockout of ER IP3receptor channels delays these signals, whereas expression of lysosomal TPC2 channels accelerates them. High-resolution Ca2+imaging reveals elementary events upon TPC2 opening and signals coupled to IP3receptors. Biasing TPC2 activation to a Ca2+-permeable state sensitizes local Ca2+signals to IP3. This increases the potency of a physiological agonist to evoke global Ca2+signals and activate a downstream target. Our data provide a conceptual framework to understand how Ca2+release from physically separated stores is coordinated.