title: Molecular mechanisms of STIM/Orai communication.
abstract: Ca(2+)entry into the cell via store-operated Ca(2+)release-activated Ca(2+)(CRAC) channels triggers diverse signaling cascades that affect cellular processes like cell growth, gene regulation, secretion, and cell death. These store-operated Ca(2+)channels open after depletion of intracellular Ca(2+)stores, and their main features are fully reconstituted by the two molecular key players: the stromal interaction molecule (STIM) and Orai. STIM represents an endoplasmic reticulum-located Ca(2+)sensor, while Orai forms a highly Ca(2+)-selective ion channel in the plasma membrane. Functional as well as mutagenesis studies together with structural insights about STIM and Orai proteins provide a molecular picture of the interplay of these two key players in the CRAC signaling cascade. This review focuses on the main experimental advances in the understanding of the STIM1-Orai choreography, thereby establishing a portrait of key mechanistic steps in the CRAC channel signaling cascade. The focus is on the activation of the STIM proteins, the subsequent coupling of STIM1 to Orai1, and the consequent structural rearrangements that gate the Orai channels into the open state to allow Ca(2+)permeation into the cell.
authors.affiliation: Institute of Biophysics, Johannes Kepler University of Linz, Linz, Austria; and.
authors.forename: Isabella
authors.initials: I
authors.lastname: Derler
authors.affiliation: Department of Physiology, University of Extremadura, Cáceres, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Jardin
authors.affiliation: Institute of Biophysics, Johannes Kepler University of Linz, Linz, Austria; and christoph.romanin@jku.at isabella.derler@jku.at.
authors.forename: Christoph
authors.identifier: http://orcid.org/0000-0003-3756-4136
authors.initials: C
authors.lastname: Romanin
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D020013:Calcium Signaling; D006801:Humans; D015640:Ion Channel Gating; D017136:Ion Transport; D008565:Membrane Proteins; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D000071740:ORAI1 Protein / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D011485:Protein Binding; D011487:Protein Conformation; D000071737:Stromal Interaction Molecule 1 / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium
keywords: CRAC channel; Orai; Orai gating; STIM-Orai interaction; STIM1
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