rac activation by the t-cell receptor inhibits t cell migrationrac激活的t细胞受体抑制t细胞迁移.pdfVIP

Rac Activation by the T-Cell Receptor Inhibits T Cell Migration ´ 1 ´ 2 3 4 5 Eva Cernuda-Morollon , Jaime Millan , Mark Shipman , Federica M. Marelli-Berg , Anne J. Ridley * ´ 1 Histocompatibility and Transplantation Unit, Hospital Universitario Central de Asturias, Oviedo, Spain, 2 Department of Cell Biology and Immunology, Centro de Biologıa Molecular Severo Ochoa, Cantoblanco, Spain, 3 Ludwig Institute for Cancer Research, University of Oxford, Oxford, United Kingdom, 4 Department of Immunology, Imperial College London, London, United Kingdom, 5 Randall Division of Cell and Molecular Biophysics, King’s College London, London, United Kingdom Abstract Background: T cell migration is essential for immune responses and inflammation. Activation of the T-cell receptor (TCR) triggers a migration stop signal to facilitate interaction with antigen-presenting cells and cell retention at inflammatory sites, but the mechanisms responsible for this effect are not known. Methodology/Principal Findings: Migrating T cells are polarized with a lamellipodium at the front and uropod at the rear. Here we show that transient TCR activation induces prolonged inhibition of T-cell migration. TCR pre-activation leads to cells with multiple lamellipodia and lacking a uropod even after removal of the TCR signal. A similar phenotype is induced by expression of constitutively active Rac1, and TCR signaling activates Rac1. TCR signaling acts via Rac to reduce phosphorylation of ezrin/radixin/moesin proteins, wh