p66Shc regulates vesicle‐mediated secretion in mast cells by affecting F‐actin dynamics

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

关键词: microvesicles;    SHIP1;    signal transduction;   

DOI  :  10.1189/jlb.0313178

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Theextracellularvesicularcompartmenthasemergedasanovelsystemofintercellularcommunication;however,themechanismsinvolvedinmembranevesiclebiogenesisandsecretionareasyetunclear.Amongimmunecellsreleasingmembranevesicles—mastcellsthatresideneartissuesexposedtotheenvironment—aremastermodulatorsofimmuneresponses.Here,wehaveaddressedtheroleofp66Shc,anovelregulatorofmastcellactivationandhomeostasis,inthedynamicreorganizationoftheactincytoskeletonthatisassociatedwithmorphologicalchangesduringsecretion.Weshowthatp66ShcisrecruitedasacomplexwiththelipidphosphataseSHIP1totheF‐actinskeletonandimpairsantigen‐dependentcorticalF‐actindisassemblyandmembranerufflingthroughtheinhibitionofVavandpaxillinphosphorylation.Wealsoshowthatinadditiontoactingasanegativeregulatorofantigen‐dependentmastcelldegranulation,p66Shclimitsthebasalreleaseofgranulecontentsbyinhibitingmicrovesiclebuddingfromtheplasmamembraneandpiecemealdegranulation.Thesefindingsidentifyp66Shcasacriticalregulatorofactindynamicsinmastcells,providingabasisforunderstandingthemolecularmechanismsinvolvedinvesicle‐mediatedsecretioninthesecells...

【 授权许可】

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