Gunaratne, Gihan S;
Kumar, Sushil;
Lin-Moshier, Yaping;
Slama, James T;
Brailiou, Eugen;
Patel, Sandip;
Walseth, Timothy F;
(2023)
Progesterone receptor membrane component 1 facilitates Ca²⁺ signal amplification between endosomes and the endoplasmic reticulum.
Journal of Biological Chemistry
, 299
(12)
, Article 105378. 10.1016/j.jbc.2023.105378.
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Abstract
Membrane contact sites (MCSs) between endosomes and the endoplasmic reticulum (ER) are thought to act as specialized trigger zones for Ca2+ signaling, where local Ca2+ released via endolysosomal ion channels is amplified by ER Ca2+-sensitive Ca2+ channels into global Ca2+ signals. Such amplification is integral to the action of the second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). However, functional regulators of inter-organellar Ca2+ crosstalk between endosomes and the ER remain poorly defined. Here, we identify progesterone receptor membrane component 1 (PGRMC1), an ER transmembrane protein that undergoes a unique heme-dependent dimerization, as an interactor of the endosomal two pore channel, TPC1. NAADP-dependent Ca2+ signals were potentiated by PGRMC1 overexpression through enhanced functional coupling between endosomal and ER Ca2+ stores and inhibited upon PGRMC1 knockdown. Point mutants in PGMRC1 or pharmacological manipulations that reduced its interaction with TPC1 were without effect. PGRMC1 therefore serves as a TPC1 interactor that regulates ER-endosomal coupling with functional implications for cellular Ca2+ dynamics and potentially the distribution of heme.
| Type: | Article |
|---|---|
| Title: | Progesterone receptor membrane component 1 facilitates Ca²⁺ signal amplification between endosomes and the endoplasmic reticulum |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jbc.2023.105378 |
| Publisher version: | https://doi.org/10.1016/j.jbc.2023.105378 |
| Language: | English |
| Additional information: | © 2023 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology under a Creative Commons license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | calcium signaling, heme, NAADP, endosomes, lysosomes |
| 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/10181333 |
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