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

Yu-Ping Lin, Daniel Bakowski, Gary R. Mirams and Anant B. Parekh ()
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Yu-Ping Lin: Oxford University
Daniel Bakowski: Oxford University
Gary R. Mirams: Nottingham University
Anant B. Parekh: Oxford University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-10329-3

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