Effect of Cavβ Subunits on Structural Organization of Cav1.2 Calcium Channels 英文参考文献.docVIP

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Effect of Cavβ Subunits on Structural Organization of Cav1.2 Calcium Channels 英文参考文献.doc

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Effect of Cavβ Subunits on Structural Organization of Cav1.2 Calcium Channels 英文参考文献

EffectofCavbSubunitsonStructuralOrganizationof Cav1.2CalciumChannels EvgenyKobrinsky.,ParwizAbrahimi.,SonQ.Duong,SamThomas,JoBethHarry,ChiragPatel,QiZong Lao,NikolaiM.Soldatov* NationalInstituteonAging,NationalInstitutesofHealth,Baltimore,Maryland,UnitedStatesofAmerica Abstract Background:Voltage-gatedCav1.2calciumchannelsplayacrucialroleinCa2+signaling.Thepore-forminga1Csubunitis regulatedbyaccessoryCavbsubunits,cytoplasmicproteinsofvarioussizeencodedbyfourdifferentgenes(Cavb1-b4 )and expressedinatissue-specificmanner. MethodsandResults:HereweinvestigatedtheeffectofthreemajorCavbtypes,b1b,b2dandb3,onthestructureofCav1.2 intheplasmamembraneoflivecells.TotalinternalreflectionfluorescencemicroscopyshowedthatthetendencyofCav1.2 to form clusters depends on the type of the Cavb subunit present. The highest density of Cav1.2 clusters in the plasma membraneandthesmallestclustersizewereobservedwithneuronal/cardiacb1bpresent.Cav1.2channelscontainingb3, thepredominantCavbsubunitofvascularsmoothmusclecells,wereorganizedinasignificantlysmallernumberoflarger clusters.Theinter-andintramoleculardistancesbetweena1CandCavbintheplasmamembraneoflivecellsweremeasured by three-color FRET microscopy. The results confirm that the proximity of Cav1.2 channels in the plasma membrane depends on the Cavb type. The presence of different Cavb subunits does not result in significant differences in the intramoleculardistancebetweentheterminiofa1C,butsignificantlyaffectsthedistancebetweentheterminiofneighbor ? ? a1C subunits,whichvariesfrom67Awithb1bto79Awithb3. Conclusions:Thus,ourresultsshowthatthestructuralorganizationofCav1.2channelsintheplasmamembranedepends onthetypeofCavbsubunitspresent. Citation:KobrinskyE,AbrahimiP,DuongSQ,ThomasS,HarryJB,etal.(2009)EffectofCavbSubunitsonStructuralOrganizationofCav1.2CalciumChannels.PLoS ONE4(5):e5587.doi:10.1371/journal.pone.0005587 Editor:ArnoldSchwartz,UniversityofCincinnati,UnitedStatesofAmerica ReceivedMarch17,2009;AcceptedApril18,2009;PublishedMay