Yuan, Yu;
Arige, Vikas;
Saito, Ryo;
Mu, Qianru;
Brailoiu, Gabriela C;
Pereira, Gustavo JS;
Bolsover, Stephen R;
... Patel, Sandip; + view all
(2024)
Two-pore channel-2 and inositol trisphosphate receptors coordinate Ca²⁺ signals between lysosomes and the endoplasmic reticulum.
Cell Reports
, 43
(1)
, Article 113628. 10.1016/j.celrep.2023.113628.
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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.
| Type: | Article |
|---|---|
| Title: | Two-pore channel-2 and inositol trisphosphate receptors coordinate Ca²⁺ signals between lysosomes and the endoplasmic reticulum |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2023.113628 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2023.113628 |
| Language: | English |
| Additional information: | Copyright © 2023 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | CP: Cell biology, Ca(2+) stores, IP(3), IP(3) receptors, NAADP, endoplasmic reticulum, histamine, lysosomes, puffs, tuffs, two-pore channels |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10184879 |
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