title: Molecular modulators of store-operated calcium entry.
abstract: Three 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.
authors.affiliation: Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Lopez
authors.affiliation: Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
authors.forename: Letizia
authors.initials: L
authors.lastname: Albarran
authors.affiliation: Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Gómez
authors.affiliation: Department of Medical Physiology and Biophysic, Institute of Biomedicine of Sevilla, Sevilla, Spain.
authors.forename: Tarik
authors.initials: T
authors.lastname: Smani
authors.affiliation: Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
authors.forename: Gines M
authors.initials: GM
authors.lastname: Salido
authors.affiliation: Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain. Electronic address: jarosado@unex.es.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rosado
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D000071739:Calcium Release Activated Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D052139:Intracellular Calcium-Sensing Proteins; D008565:Membrane Proteins / Q000502:physiology; D008954:Models, Biological; D000071740:ORAI1 Protein / Q000502:physiology; D011487:Protein Conformation; D021122:Protein Subunits; D000071737:Stromal Interaction Molecule 1 / Q000502:physiology; D050052:TRPC Cation Channels / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D000071739:Calcium Release Activated Calcium Channels; D052139:Intracellular Calcium-Sensing Proteins; D008565:Membrane Proteins; D000071740:ORAI1 Protein; D021122:Protein Subunits; C572578:SARAF protein, human; C000604313:STIMATE protein, human; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; D002118:Calcium
keywords: CRACR2A; Golli; ORMDL3; Orai1; SARAF; STIM1; Septin; Store-operated calcium entry