Rac Activation by the T-Cell Receptor Inhibits T Cell Migration 英文参考文献.docVIP

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Rac Activation by the T-Cell Receptor Inhibits T Cell Migration 英文参考文献.doc

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Rac Activation by the T-Cell Receptor Inhibits T Cell Migration 英文参考文献

RacActivationbytheT-CellReceptorInhibitsTCell Migration EvaCernuda-Morollo′n1,JaimeMilla′n2,MarkShipman3,FedericaM.Marelli-Berg4,AnneJ.Ridley5* 1HistocompatibilityandTransplantationUnit,HospitalUniversitarioCentraldeAsturias,Oviedo,Spain,2DepartmentofCellBiologyandImmunology,CentrodeBiolog?′a Molecular Severo Ochoa, Cantoblanco, Spain, 3Ludwig Institute for Cancer Research, University of Oxford, Oxford, United Kingdom, 4Department of Immunology, ImperialCollegeLondon,London,UnitedKingdom,5RandallDivisionofCellandMolecularBiophysics,King’sCollegeLondon,London,UnitedKingdom Abstract Background:Tcellmigrationisessentialforimmuneresponsesandinflammation.ActivationoftheT-cellreceptor(TCR) triggers a migration stop signal to facilitate interaction with antigen-presenting cells and cell retention at inflammatory sites,butthemechanismsresponsibleforthiseffectarenotknown. Methodology/PrincipalFindings:MigratingTcellsarepolarizedwithalamellipodiumatthefrontanduropodattherear. HereweshowthattransientTCRactivationinducesprolongedinhibitionofT-cellmigration.TCRpre-activation leadsto cellswithmultiplelamellipodiaandlackingauropodevenafterremovaloftheTCRsignal.Asimilarphenotypeisinduced by expression of constitutively active Rac1, and TCR signaling activates Rac1. TCR signaling acts via Rac to reduce phosphorylation of ezrin/radixin/moesin proteins, which are required for uropod formation, and to increase stathmin phosphorylation,whichregulatesmicrotubulestability.TcellpolarityandmigrationispartiallyrestoredbyinhibitingRacor byexpressingconstitutivelyactivemoesin. Conclusions/Significance:WeproposethattransientTCRsignalinginducessustainedinhibitionofTcellmigrationviaRac1, increasedstathminphosphorylationandreducedERMphosphorylationwhichacttogethertoinhibitT-cellmigratorypolarity. Citation: Cernuda-Morollo′n E, Milla′n J, Shipman M, Marelli-Berg FM, Ridley AJ (2010) Rac Activation by the T-Cell Receptor Inhibits T Cell Migration. PLoS ONE5(8):e12393.doi:10.1371/journal.po