Calcium-Dependent Increases in Protein Kinase-A Activity in Mouse Retinal Ganglion Cells Are Mediated by Multiple Adenylate Cyclases 英文参考文献.docVIP

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Calcium-Dependent Increases in Protein Kinase-A Activity in Mouse Retinal Ganglion Cells Are Mediated by Multiple Adenylate Cyclases 英文参考文献.doc

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Calcium-Dependent Increases in Protein Kinase-A Activity in Mouse Retinal Ganglion Cells Are Mediated by Multiple Adenylate Cyclases 英文参考文献

Calcium-DependentIncreasesinProteinKinase-A ActivityinMouseRetinalGanglionCellsAreMediatedby MultipleAdenylateCyclases TimothyA.Dunn1,DanielR.Storm2,MarlaB.Feller3* 1NeurobiologySection,DivisionofBiologicalSciences,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica,2DepartmentofPharmacology, University of Washington, Seattle, Washington, United States of America, 3Department of Molecular and Cell Biology and the Helen Wills Neuroscience Institute, UniversityofCalifornia,Berkeley,California,UnitedStatesofAmerica Abstract Neuronsundergolongterm,activitydependentchangesthataremediatedbyactivationofsecondmessengercascades.In particular,calcium-dependentactivationofthecyclic-AMP/ProteinkinaseAsignalingcascadehasbeenimplicatedinseveral developmentalprocessesincludingcellsurvival,axonaloutgrowth,andaxonalrefinement.Thebiochemicallinkbetween calciuminfluxandtheactivationofthecAMP/PKApathwayisprimarilymediatedthroughadenylatecyclases.Here,dual imagingofintracellularcalciumconcentrationandPKAactivitywasusedtoassaytheroleofdifferentclassesofcalcium- dependentadenylatecyclases(ACs)intheactivationofthecAMP/PKApathwayinretinalganglioncells(RGCs).Surprisingly, depolarization-inducedcalcium-dependentPKAtransientspersistinbarrellessmicelackingAC1,thepredominantcalcium- dependentadenylate cyclasein RGCs, as wellas in double knockout mice lacking both AC1and AC8.Furthermore, in a subsetofRGCs,depolarization-inducedPKAtransientspersistduringtheinhibitionofalltransmembraneadenylatecyclases. These results are consistent with the existence of a soluble adenylate cyclase that plays a role in calcium-dependent activationofthecAMP/PKAcascadeinneurons. Citation: Dunn TA, Storm DR, Feller MB (2009) Calcium-Dependent Increases in Protein Kinase-A Activity in Mouse Retinal Ganglion Cells Are Mediated by MultipleAdenylateCyclases.PLoSONE4(11):e7877.doi:10.1371/journal.pone.0007877 Editor:MichaelHendricks,HarvardUniversity,UnitedStatesofAmerica ReceivedSeptember4,2009;Accept