Involvement of the Wiskott-Aldrich syndrome protein and other actin regulatory adaptors in T cell activation

Abstract

The actin cytoskeleton is a dynamic structure recognized for many years as integral to the coupling of external stimuli to cell activation and ensuing changes in morphology and movement. It is only recently, however, that a molecular understanding of actin involvement in these activities has emerged coincident with the identification of cytosolic signaling effectors that couple extracellular stimuli to induction of actin nucleation. Notable among these actin regulatory effectors are members of the Wiskott-Aldrich syndrome protein (WASp) family, a group of cytoskeletal adaptors imbued with the capacity to connect various signal transduction pathways to the Arp 2/3 complex and Arp 2/3-mediated actin polymerization. In T cells, the functional characterization of WASp and other actin-modulatory adaptors has proved instrumental in delineating the molecular interactions evoking actin cytoskeletal reorganization downstream of antigen receptor engagement and in clarifying the influence of actin-based processes on T cell activation. In this review, the structural and functional properties of the major actin regulatory cytoskeletal adaptors in T cells are described with an emphasis on the roles of these proteins in fostering the TCR actin cytoskeletal interplay required for induction of T cell activation and expression of dynamic effector responses.