title: The ER/PM microdomain, PI(4,5)P₂ and the regulation of STIM1-Orai1 channel function.
abstract: All forms of cell signaling occur in discreet cellular microdomains in which the ER is the main participant and include microdomains formed by the ER with lysosomes, endosomes, the nucleus, mitochondria and the plasma membrane. In the microdomains the two opposing organelles transfer and exchange constituents including lipids and ions. As is the case for other forms of signaling pathways, many components of the receptor-evoked Ca(2+) signal are clustered at the ER/PM microdomain, including the Orai1-STIM1 complex. This review discusses recent advances in understanding the molecular components that tether the ER and plasma membrane to form the ER/PM microdomains in which PI(4,5)P2 is enriched, and how dynamic targeting of the Orai1-STIM1 complex to PI(4,5)P2-poor and PI(4,5)P2-rich microdomains controls the activity of Orai1 and its regulation by Ca(2+) that is mediated by SARAF.
authors.affiliation: Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD 20892, United States.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Physiology, College of Medicine, Chosun University, 501-375, Republic of Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.affiliation: First Department of Medicine, University of Szeged, Szeged H-6725, Hungary.
authors.forename: Jozsef J
authors.initials: JJ
authors.lastname: Maléth
authors.affiliation: Department of Physiology, School of Medicine, Ewha Womans University, 911-1 Mok-6-dong, Yang Chun-gu, Seoul 158-710, Republic of Korea.
authors.forename: Seonghee
authors.initials: S
authors.lastname: Park
authors.affiliation: Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD 20892, United States.
authors.forename: Malini
authors.initials: M
authors.lastname: Ahuja
authors.affiliation: Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD 20892, United States. Electronic address: shmuel.muallem@nih.gov.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Muallem
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium
keywords: Calcium signaling; ER/PM microdomains; Orai1; Stim1
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