Distinct Contributions of Orai1 and TRPC1 to Agonist-Induced [Ca2+]i Signals Determine Specificity of Ca2+-Dependent Gene Expression 英文参考文献.docVIP

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Distinct Contributions of Orai1 and TRPC1 to Agonist-Induced [Ca2+]i Signals Determine Specificity of Ca2+-Dependent Gene Expression 英文参考文献.doc

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DistinctContributionsofOrai1andTRPC1toAgonist-Induced[Ca2]iSignalsDetermineSpecificityofCa2-DependentGeneExpression英文参考文献

DistinctContributionsofOrai1andTRPC1toAgonist- Induced[Ca ]iSignalsDetermineSpecificityofCa - DependentGeneExpression 2+ 2+ HweiLingOng,Shyh-IngJang,InduSureshAmbudkar* Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda,Maryland,UnitedStatesofAmerica Abstract Regulation of critical cellular functions, including Ca2+-dependent gene expression, is determined by the temporal and spatial aspects of agonist-induced Ca signals. Stimulation of cells with physiological concentrations of agonists trigger 2+ increases[Ca ]iduetointracellularCa releaseandCa2+influx.WhileOrai1-STIM1channelsaccountforagonist-stimulated 2+ 2+ 2+ [Ca ]iincreaseaswellasactivationofNFATincellssuchaslymphocytes,RBLandmastcells,bothOrai1-STIM1andTRPC1- 2+ STIM1channelscontributeto[Ca ]iincreasesinhumansubmandibulargland(HSG)cells.However,onlyOrai1-mediated 2+ 2+ entryregulatestheactivationofNFATinHSGcells.SincebothTRPC1andOrai1areactivatedfollowinginternalCa 2+ Ca storedepletioninthesecells,itisnotclearhowthecellsdecodeindividualCa signalsgeneratedbythetwochannelsfor the regulation of specific cellular functions. Here we have examined the contributions of Orai1 and TRPC1 to carbachol 2+ 2+ (CCh)-induced [Ca ]i signals and activation of NFAT in single cells. We report that Orai1-mediated Ca entry generates 2+ 2+ [Ca ]i oscillations at different [CCh], ranging from very low to high. In contrast, TRPC1-mediated Ca entry generates 2+ 2+ sustained [Ca ]i elevation at high [CCh] and contributes to frequency of [Ca ]i oscillations at lower [agonist]. More importantly,thetwochannelsarecoupledtoactivationofdistinctCa dependentgeneexpressionpathways,consistent 2+ 2+ withthedifferentpatternsof[Ca ]isignalsmediatedbythem.NucleartranslocationofNFATandNFAT-dependentgene 2+ expression display ‘‘all-or-none’’ activation that is exclusively driven by local [Ca ]i genera