Yu-Ping Lin
Selective recruitment of different Ca2+-dependent transcription factors by STIM1-Orai1 channel clusters
Lin, Yu-Ping; Bakowski, Daniel; Mirams, Gary R.; Parekh, Anant B.
Authors
Daniel Bakowski
Prof. GARY MIRAMS GARY.MIRAMS@NOTTINGHAM.AC.UK
Professor of Mathematical Biology
Anant B. Parekh
Abstract
© 2019, The Author(s). Store-operated Ca2+ entry, involving endoplasmic reticulum Ca2+ sensing STIM proteins and plasma membrane Orai1 channels, is a widespread and evolutionary conserved Ca2+ influx pathway. This form of Ca2+ influx occurs at discrete loci where peripheral endoplasmic reticulum juxtaposes the plasma membrane. Stimulation evokes numerous STIM1-Orai1 clusters but whether distinct signal transduction pathways require different cluster numbers is unknown. Here, we show that two Ca2+-dependent transcription factors, NFAT1 and c-fos, have different requirements for the number of STIM1-Orai1 clusters and on the Ca2+ flux through them. NFAT activation requires fewer clusters and is more robustly activated than c-fos by low concentrations of agonist. For similar cluster numbers, transcription factor recruitment occurs sequentially, arising from intrinsic differences in Ca2+ sensitivities. Variations in the number of STIM1-Orai1 clusters and Ca2+ flux through them regulate the robustness of signalling to the nucleus whilst imparting a mechanism for selective recruitment of different Ca2+-dependent transcription factors.
Citation
Lin, Y., Bakowski, D., Mirams, G. R., & Parekh, A. B. (2019). Selective recruitment of different Ca2+-dependent transcription factors by STIM1-Orai1 channel clusters. Nature Communications, 10(1), https://doi.org/10.1038/s41467-019-10329-3
Journal Article Type | Article |
---|---|
Acceptance Date | Apr 23, 2019 |
Online Publication Date | Jun 7, 2019 |
Publication Date | 2019-12 |
Deposit Date | Jun 13, 2019 |
Publicly Available Date | Jun 13, 2019 |
Journal | Nature Communications |
Electronic ISSN | 2041-1723 |
Publisher | Nature Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 10 |
Issue | 1 |
Article Number | 2516 |
DOI | https://doi.org/10.1038/s41467-019-10329-3 |
Keywords | General Biochemistry, Genetics and Molecular Biology; General Physics and Astronomy; General Chemistry |
Public URL | https://nottingham-repository.worktribe.com/output/2185175 |
Publisher URL | https://www.nature.com/articles/s41467-019-10329-3 |
Additional Information | Received: 30 May 2018; Accepted: 23 April 2019; First Online: 7 June 2019; : A.B.P. is Scientific Founder of Calcico Therapeutics. The remaining authors declare no competing interests. |
Files
s41467-019-10329-3
(3.8 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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