Pivotal Advance: Phospholipids determine net membrane surface charge resulting in differential localization of active Rac1 and Rac2

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

关键词: neutrophils;    phagocytosis;    chemotaxis;   

DOI  :  10.1189/jlb.0609390

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inthisinvestigation,weusedprimarymurineneutrophilstodemonstratethatlocalchangesinmembranephospholipidcompositionalterthenetcytoplasmicmembranesurfacecharge,whichresultsinselectiverecruitmentofRac1orRac2basedonthenetchargeoftheirrespectiveC‐terminaldomains.MurineneutrophilsundergoingchemotaxisorcarryingoutphagocytosisweretransfectedwithK‐ras4B‐derivedmembranechargebiosensorsandlipidmarkers,whichallowedustosimultaneouslymonitorthelevelsofPIP2,PIP3,andPSandnetmembranechargeofthenewlydevelopingphagosomemembraneandplasmamembrane.OurresultsindicatethatthecombinationofPIP2,PIP3,andPSgeneratesahighnegativecharge(–8)attheplasmamembraneofactin‐richpseudopods,whereactiveRac1preferentiallylocalizesduringphagosomeformation.ThelipidmetabolismthatoccursduringphagosomematurationresultsinthelocalizeddepletionofPIP2,PIP3,andpartialdecreaseinPS.ThiscreatesamoderatelynegativenetchargethatcorrelateswiththelocalizationofactiveRac2.Conversely,theaccumulationofPIP3attheleading‐edgemembraneduringchemotaxisgeneratesapolarizedaccumulationofnegativechargesthatrecruitsRac1.Theseresultsprovideevidencethatalterationsinmembranelipidcompositionandinner‐membranesurfacechargeareimportantelementsfortherecruitmentofdifferentiallychargedproteinsandlocalizationofsignalingpathwaysduringphagocytosisandchemotaxisinneutrophils...

【 授权许可】

CC BY