{Reference Type}: Journal Article
{Title}: Two-pore channel-2 and inositol trisphosphate receptors coordinate Ca2+ signals between lysosomes and the endoplasmic reticulum.
{Author}: Yuan Y;Arige V;Saito R;Mu Q;Brailoiu GC;Pereira GJS;Bolsover SR;Keller M;Bracher F;Grimm C;Brailoiu E;Marchant JS;Yule DI;Patel S;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 1
{Year}: 2024 01 23
暂无{DOI}: 10.1016/j.celrep.2023.113628
{Abstract}: 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 IP3 receptor 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 IP3 receptors. 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.