title: Store-operated Ca2+ Entry-associated Regulatory factor (SARAF) Plays an Important Role in the Regulation of Arachidonate-regulated Ca2+ (ARC) Channels.
abstract: The store-operated Ca(2+)entry-associated regulatory factor (SARAF) has recently been identified as a STIM1 regulatory protein that facilitates slow Ca(2+)-dependent inactivation of store-operated Ca(2+)entry (SOCE). Both the store-operated channels and the store-independent arachidonate-regulated Ca(2+)(ARC) channels are regulated by STIM1. In the present study, we show that, in addition to its location in the endoplasmic reticulum, SARAF is constitutively expressed in the plasma membrane, where it can interact with plasma membrane (PM)-resident ARC forming subunits in the neuroblastoma cell line SH-SY5Y. Using siRNA-based and overexpression approaches we report that SARAF negatively regulates store-independent Ca(2+)entry via the ARC channels. Arachidonic acid (AA) increases the association of PM-resident SARAF with Orai1. Finally, our results indicate that SARAF modulates the ability of AA to promote cell survival in neuroblastoma cells. In addition to revealing new insight into the biology of ARC channels in neuroblastoma cells, these findings provide evidence for an unprecedented location of SARAF in the plasma membrane.
authors.affiliation: From the Department of Physiology (Cellular Physiology Research Group), University of Extremadura, 10003 Caceres, Spain and.
authors.forename: Letizia
authors.initials: L
authors.lastname: Albarran
authors.affiliation: From the Department of Physiology (Cellular Physiology Research Group), University of Extremadura, 10003 Caceres, Spain and.
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Lopez
authors.affiliation: Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Geoffrey E
authors.initials: GE
authors.lastname: Woodard
authors.affiliation: From the Department of Physiology (Cellular Physiology Research Group), University of Extremadura, 10003 Caceres, Spain and.
authors.forename: Gines M
authors.initials: GM
authors.lastname: Salido
authors.affiliation: From the Department of Physiology (Cellular Physiology Research Group), University of Extremadura, 10003 Caceres, Spain and jarosado@unex.es.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rosado
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D052139:Intracellular Calcium-Sensing Proteins; D017136:Ion Transport; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000071740:ORAI1 Protein; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D052139:Intracellular Calcium-Sensing Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C522867:Orai3 protein, human; D034741:RNA, Small Interfering; C572578:SARAF protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D016718:Arachidonic Acid; D002118:Calcium
keywords: ARC channels; SARAF; arachidonic acid (AA) (ARA); calcium channel; calcium release-activated calcium channel protein 1 (ORAI1); protein-protein interaction; stromal interaction molecule 1 (STIM1)
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