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.
Journal article
Nat Commun
07/06/2019
10
Animals, Calcium, Calcium Signaling, Cell Line, Cell Membrane, Endoplasmic Reticulum, NFATC Transcription Factors, ORAI1 Protein, Proto-Oncogene Proteins c-fos, Rats, Signal Transduction, Stromal Interaction Molecule 1