gababr在细胞膜上的运动机制分析-analysis of gaba br movement mechanism on cell membrane.docx

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2018-06-04 发布于上海
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gababr在细胞膜上的运动机制分析-analysis of gaba br movement mechanism on cell membrane.docx

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gababr在细胞膜上的运动机制分析-analysis of gaba br movement mechanism on cell membrane

AbstractGABABreceptorsaremembersofclassCfamilyofGproteincoupledreceptors,and theirligandisinhibitoryneurotransmittergamma-aminobutyricacid(GABA)ofthecentral nervoussystem.GABABreceptorsconsistofGABAB1andGABAB2subunits.GABABreceptorsarewidely distributedinmammaliancentral nervoussystem andperipheral nervous systemandmedicated slowsynapticinhibitioninthebrain.PreviousresearchesinourlabshowedthatGABABreceptorsarelocatedinlipidrafts intherestingstateofthecell,andthepalmitoylationofGABAB2C-tailplaysanimportant roleinit.WhentheGABABreceptorshavebeenactivated,theywilltransferoutoflipid rafts.Receptorsassociatedwithlipidraftshaveasignificantinfluenceonitssignal transduction.Whethertheactivityofthe receptors candynamicallyregulatethe palmitoyationofGABABreceptorsandpalmitoylationcanregulatethereceptorsthrough otherpost-translationproteinmodifications,thereis notmuchresearchaboutit.InHEK293cellsandCGNs,throughtheABEexperiments,wefoundthattheCys874 on theGABAB2C-tailcouldoccurthepalmitoylation,whichisregulatedby theactivityof thereceptors.WhentheGABABreceptorshavebeenactivated,thepalmitoylationofthe receptors willbe reduced,andatthesame timeGABABR willtransferoutoflipid.Through thesequenceanalysis,wefoundthatneartheCys874oftheGABAB2C-tailisYQEL, whichismostlyAP2bindingmotif,andtheYmaybeapotentialphosphorylationsiteof non-receptortyrosinekinase.SowespeculatethatpalmitoylationofGABABreceptorson theGABAB2C-tailensurespropersurfacelocationandincreasesthestabilityofGABABreceptorsinthecellsurfaceviatyrosinephosphorylationoftyrosinebasedinternalization motifs.StudieshaveshownthatGABAB2C-tailisplayingadominantroleinregulatingthe internalizationofGABABreceptorsinlivecells.Ourresultsfurtherprovethatwhenwe mutatedsitesofGABAB2C-tailYQEL,itwillblocktheinternalizationofreceptorsand destroy the interaction with receptors and non-receptor tyrosine kinase. So we got aconclusionthatTyrsine830maybethephosphorylationsiteanditsinteractionwith palmitoylationofCys874willinfluencethereceptorsconsti