Nuclear phospholipid scramblase 1 prolongs the mitotic expansion of granulocyte precursors during G‐CSF‐induced granulopoiesis

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

关键词: PLSCR1;    emergency granulopoiesis;    cell cycle;    mitosis;    nuclear trafficking;   

DOI  :  10.1189/jlb.0111006

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

PLSCR1−/−miceexhibitnormal,steady‐statehematologicparametersbutimpairedemergencygranulopoiesisuponinvivoadministrationofG‐CSF.ThemechanismbywhichPLSCR1contributestoG‐CSF‐inducedneutrophilproductionislargelyunknown.WenowreportthattheexpansionofbonemarrowmyelocytesuponinvivoG‐CSFtreatmentisreducedinPLSCR1−/−micerelativetoWT.UsingSCF‐ER‐Hoxb8‐immortalizedmyeloidprogenitorstoexaminetheprogressionofG‐CSF‐drivengranulocyticdifferentiationinvitro,wefoundthatPLSCR1prolongstheperiodofmitoticexpansionofproliferativegranulocyteprecursors,therebygivingrisetoincreasedneutrophilproductionfromtheirprogenitors.ThiseffectofPLSCR1isblockedbyaΔNLS‐PLSCR1,whichpreventsitsnuclearimport.Bycontrast,mutationthatpreventsthemembraneassociationofPLSCR1hasminimalimpactontheroleofPLSCR1inG‐CSF‐inducedgranulopoiesis.ThesedataimplythatthecapacityofPLSCR1toaugmentG‐CSF‐dependentproductionofmatureneutrophilsfrommyeloidprogenitorsisunrelatedtoitsreportedactivitiesattheendofacialsurfaceoftheplasmamembranebutdoesrequireentryoftheproteinintothenucleus,suggestingthatthisresponseismediatedthroughtheobservedeffectsofPLSCR1ongenetranscription...

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