title: Key components of store-operated Ca2+ entry in non-excitable cells.
abstract: Store-operated Ca(2+) entry (SOCE) is a ubiquitous Ca(2+) entry pathway in non-excitable cells. It is activated by the depletion of Ca(2+) from intracellular Ca(2+) stores, notably the endoplasmic reticulum (ER). In the past 9 years, it has been established that two key proteins, stromal interacting molecule 1 (STIM1) and Orai1, play critical roles in SOCE. STIM1 is a single-pass transmembrane protein located predominantly in the ER that serves as a Ca(2+) sensor within the ER, while Orai1 is a tetraspanning plasma membrane (PM) protein that functions as the pore-forming subunit of store-operated Ca(2+) channels. A decrease in the ER Ca(2+) concentration induces translocation of STIM1 into puncta close to the PM. STIM1 oligomers directly interact with Orai1 channels and activates them. This review summarizes the molecular basis of the interaction between STIM1 and Orai1 in SOCE. Further, we describe current findings on additional regulatory proteins, such as Ca(2+) release-activated Ca(2+) regulator 2A and septin, novel roles of STIM1, and modulation of SOCE by protein phosphorylation.
authors.affiliation: Department of Pharmacology, School of Dentistry, Health Sciences University of Hokkaido, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tojyo
authors.forename: Takao
authors.initials: T
authors.lastname: Morita
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nezu
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tanimura
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020555:GTP-Binding Protein Regulators; D006801:Humans; D052139:Intracellular Calcium-Sensing Proteins / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D000071740:ORAI1 Protein; D014176:Protein Biosynthesis; D058112:Septins / Q000502:physiology; D000071737:Stromal Interaction Molecule 1
chemical_list: C551025:CRACR2A protein, human; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D020555:GTP-Binding Protein Regulators; D052139:Intracellular Calcium-Sensing Proteins; C519056:Jpk protein, mouse; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D058112:Septins; D002118:Calcium