Regulation of macrophage motility by Irgm1

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

关键词: innate immunity;    trafficking;    migration;    interferon;    macrophage;   

DOI  :  10.1189/jlb.0509299

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

IRGareafamilyofIFN‐regulatedproteinsthatarecriticalforresistancetoinfection.MouseIRGproteinsaredividedintoGMSandGKSsubfamilies,basedonasequencewithintheG1GTP‐bindingmotif.TheGMSproteinshaveaparticularlyprofoundimpactonimmunity,astypifiedbyIrgm1,ofwhichabsenceleadstoacompletelossofresistancetoavarietyofintracellularbacteriaandprotozoa.Theunderlyingmolecularandcellularmechanismsarenotclear.Here,weusetime‐lapsemicroscopyandcell‐trackinganalysistodemonstratethatIrgm1isrequiredformotilityofIFN‐γ‐activatedmacrophages.TheabsenceofIrgm1ledtodecreasedactinremodelingattheleadingedgeofmigratingmacrophages,aswellasdecreasedRacactivation.AlthoughIrgm1didnotlocalizetotheleadingedgeofmigratingmacrophages,itwasfoundtoregulatethelocalizationofaGKSIRGprotein,Irgb6,whichinturn,concentratedontheplasmamembraneintheadvancinglamellipodia,incloseappositiontomolecularcomponentsthatregulatemembraneremodeling,includingRac,paxillin,andactin.Thus,Irgm1likelycontrolsmacrophagemotilitybyregulatingthepositioningofspecificGKSIRGproteinstotheplasmamembrane,whichinturn,modulatecytoskeletalremodelingandmembranedynamics...

【 授权许可】

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