Document Type
Article
Publication Date
12-30-2023
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.
Recommended Citation
Yuan, Yu; Arige, Vikas; Saito, Ryo; Mu, Qianru; Brailoiu, Gabriela C.; Pereira, Gustavo J.S.; Bolsover, Stephen R.; Keller, Marco; Bracher, Franz; Grimm, Christian; Brailoiu, Eugen; Marchant, Jonathan S.; Yule, David I.; and Patel, Sandip, "Two-Pore Channel-2 and Inositol Trisphosphate Receptors Coordinate CA2+ Signals Between Lysosomes and the Endoplasmic Reticulum" (2023). College of Pharmacy Faculty Papers. Paper 54.
https://jdc.jefferson.edu/pharmacyfp/54
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
38160394
Language
English
Comments
This article is the author's final published version in Cell Reports, Volume 43, Issue 1, 23 January 2024, Article number 113628.
The published version is available at https://doi.org/10.1016/j.celrep.2023.113628. Copyright © 2023 The Author(s).