Lopez, Jose JAlbarran, LetiziaGómez, Luis JSmani, TarikSalido, Gines MRosado, Juan A2023-01-252023-01-252016-04-270006-3002http://hdl.handle.net/10668/10040Three decades ago, store-operated Ca(2+) entry (SOCE) was identified as a unique mechanism for Ca(2+) entry through plasma membrane (PM) Ca(2+)-permeable channels modulated by the intracellular Ca(2+) stores, mainly the endoplasmic reticulum (ER). Extensive analysis of the communication between the ER and the PM leads to the identification of the protein STIM1 as the ER-Ca(2+) sensor that gates the Ca(2+) channels in the PM. Further analysis on the biophysical, electrophysiological and biochemical properties of STIM1-dependent Ca(2+) channels has revealed the presence of a highly Ca(2+)-selective channel termed Ca(2+) release-activated Ca(2+) channel (CRAC), consisting of Orai1 subunits, and non-selective cation channels named store-operated channels (SOC), including both Orai1 and TRPC channel subunits. Since the identification of the key elements of CRAC and SOC channels a number of intracellular modulators have been reported to play essential roles in the stabilization of STIM-Orai interactions, collaboration with STIM1 conformational changes or mediating slow Ca(2+)-dependent inactivation. Here, we review our current understanding of some of the key modulators of STIM1-Orai1 interaction, including the proteins CRACR2A, STIMATE, SARAF, septins, golli and ORMDL3.enCRACR2AGolliORMDL3Orai1SARAFSTIM1SeptinStore-operated calcium entryAnimalsCalciumCalcium ChannelsCalcium Release Activated Calcium ChannelsCalcium SignalingEndoplasmic ReticulumHumansIntracellular Calcium-Sensing ProteinsMembrane ProteinsModels, BiologicalORAI1 ProteinProtein ConformationProtein SubunitsStromal Interaction Molecule 1TRPC Cation Channelsresearch article27130253open access10.1016/j.bbamcr.2016.04.024https://doi.org/10.1016/j.bbamcr.2016.04.024