Fig. 1. Actin regulatory pathways during T-cell activation by antigen-presenting cells. The drawing shows the formation of the immunological synapse (IS) at the T-cell–APC interface, and the distal pole complex (DPC) at the opposite face of the T cell. Both complexes are organized in part by actin filaments. TCR stimulation recruits the actin regulators WASp/WIP, WAVE2 and HS1 to the IS, and pathways involving specific kinases, adapter molecules and Rho GTPases activate Arp2/3-complex-dependent polymerization of branched actin filaments. In parallel, engagement of the co-stimulatory molecules CD2 and CD28 induces dephosphorylation and activation of cofilin. The severing activity of cofilin disassembles filaments to monomers and generates new barbed ends for filament elongation, a process that further enhances actin polymerization at the IS. TCR stimulation also induces transient dephosphorylation of the ERM proteins ezrin and moesin, leading to the release of these proteins from actin filaments and plasma membrane binding proteins. Subsequent rephosphorylation of ERM proteins is coupled by unknown mechanisms to their movement away from the site of TCR engagement. This process allows ERM proteins to attach to their cargo molecules (which include both cell surface and cytoplasmic proteins), near the IS and then sweep these molecules rearward to form the DPC.