Caveolin-1-Mediated Apolipoprotein A-I Membrane Binding Sites Are Not Required for Cholesterol Efflux 英文参考文献.docVIP

Caveolin-1-MediatedApolipoproteinA-IMembrane BindingSitesAreNotRequiredforCholesterolEfflux SoazigLeLay1,MacarenaRodriguez2,WendyJessup2,CarlesRentero2¤,QiongLi2,Sia?nCartland2, ThomasGrewal3,KatharinaGaus2* 1Centre de Recherche des Cordeliers, INSERM, U872, Paris, France, 2Centre for Vascular Research, University of New South Wales, Sydney, Australia, 3Faculty of Pharmacy,UniversityofSydney,Sydney,Australia Abstract Caveolin-1(Cav1),astructuralproteinrequiredfortheformationofinvaginatedmembranedomainsknownascaveolae,has beenimplicatedincholesteroltraffickingandhomeostasis.HereweinvestigatedthecontributionofCav1toapolipoprotein A-I(apoA-I)cellsurfacebindingandintracellularprocessingusingmouseembryonicfibroblasts(MEFs)derivedfromwild type(WT)orCav1-deficient(Cav12/2)animals.WefoundthatcellsexpressingCav1have2.6-foldmoreapoA-Ibindingsites thanCav12/2cellsalthoughtheseadditionalbindingsitesarenotassociatedwithdetergent-freelipidrafts.Further,Cav1- mediatedbindingtargetsapoA-Iforinternalizationanddegradationandtheseprocessesarenotcorrelatedtocholesterol efflux. Despite lower apoA-I binding, cholesterol efflux from Cav12/2 MEFs is 1.7-fold higher than from WT MEFs. StimulationofABCA1expressionwithanLXRagonistenhancescholesteroleffluxfrombothWTandCav12/2cellswithout increasing apoA-I surface binding or affecting apoA-I processing. Our results indicate that there are at least two independentlipidbindingsitesforapoA-I;Cav1-mediatedapoA-Isurfacebindinganduptakeisnotlinkedtocholesterol efflux,indicatingthatmembranedomainsotherthancaveolaeregulateABCA1-mediatedcholesterolefflux. Citation:LeLayS,RodriguezM,JessupW,RenteroC,LiQ,etal.(2011)Caveolin-1-MediatedApolipoproteinA-IMembraneBindingSitesAreNotRequiredfor CholesterolEfflux.PLoSONE6(8):e23353.doi:10.1371/journal.pone.0023353 Editor:LudgerJohannes,InstitutCurie,France ReceivedMay30,2011;AcceptedJuly13,2011;PublishedAugust12,2011 Copyright: ? 2011 Le Lay et al. This is an open-access article distributed under the terms of t