DAP12 impacts trafficking and surface stability of killer immunoglobulin‐like receptors on natural killer cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: innate immunity;    receptor maturation;    receptor internalization;   

DOI  :  10.1189/jlb.0213093

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

KIRaidintheregulationofNKcellactivity.Inthisstudy,theeffectoftheinteractionbetweentheKIR2DSandtheiradapter,DAP12,wasinvestigatedbeyondthepreviouslydefinedsignalingfunction.FlowcytometryanalysisshowedenhancedKIR2DSsurfaceexpressiononNKLcellswhencotransfectedwithDAP12.Conversely,KIR2DS4surfaceexpressiononprimarycellswasdecreasedwhenthecellsweretreatedwithDAP12‐specificsiRNA.TreatmentoftheKIR2DSandDAP12‐transfectedcellswithCHXorBFArepressedKIR2DSsurfaceexpression,revealingaroleforDAP12intraffickingnewlysynthesizedKIRtothecellsurface.ImmunoprecipitationofDAP12revealedaninteractionofDAP12withanimmatureisoformofKIR2DS,indicatingthattheinteractionlikelyinitiateswithintheER.AninternalizationassaydemonstratedasignificantimpactofDAP12onKIR2DSsurfacestability.ConfocalmicroscopyshowedthatinternalizedKIR2DSmoleculesarerecruitedtolysosomalcompartmentsindependentofDAP12expression.OurresultssuggestthatinvivoconditionsthatadverselyaffectDAP12expressionwillindirectlyreducesurfaceexpressionandstabilityofKIR2DS.TheseeffectscouldsignificantlyimpactligandrecognitionandstrengthofsignalingthroughKIR2DSmolecules...

【 授权许可】

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