| An efficient immune system is dependent on many circulating populations of specialized cells. T cells are one specialized population continuously patrolling the body by trafficking between the blood and lymphoid organs. The process of trafficking requires several highly dynamic and coordinated changes in cyto-architecture, including the formation of a tail-like structure, a uropod. One family of proteins involved in many cytoskeletal changes is the ezrin, radixin and moesin (ERM) family of actin-binding proteins. These studies investigated the role of ERM proteins, ezrin and moesin, in T cell adhesion and migration, as well as flotillins as a family of potential regulators. The role of ERM proteins is elucidated using ezrin and moesin-deficient T cells, and generated from mice with a conditional deletion of ezrin in CD4 + cells and moesin-specific siRNA. ERM-deficient T cells migrated normally in multiple in vitro and in vivo assays, and could undergo efficient diapedesis in vitro. However, these cells were impaired in their ability to adhere to β1 integrin ligand, fibronectin, and to polarize appropriately in response to fibronectin and VCAM-1 engagement. ERM proteins are specifically required for β1-mediated integrin functions since they are dispensable in T cell adhesion and polarization in response to β2 ligand, ICAM-1. In vivo, ERM-deficient T cells showed defects in homing to lymphoid organs. These studies also investigated flotillins as potential regulators of ERM protein polarity using flotillin-specific siRNA. Flotillin-deficient T cells were impaired in their ability to polarize appropriately in response to fibronectin. In addition, ERM proteins in flotillin-deficient T cells were also impaired in their ability to polarize. Together, these results show that ERM proteins are largely dispensable for T cell chemotaxis, are important for β1 integrin function and homing to lymphoid organs, and that flotillins are potential regulators of ERM polarity. |
