Selective recruitment of different Ca2+-dependent transcription factors by STIM1-Orai1 channel clusters

Lin, Yu-Ping; Bakowski, Daniel; Mirams, Gary R.; Parekh, Anant B.

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.-P., 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), Article 2516. 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.
• Contract Date: Jun 13, 2019