title: Wiskott-Aldrich syndrome protein--dynamic regulation of actin homeostasis: from activation through function and signal termination in T lymphocytes.
abstract: The actin cytoskeleton network forms a key link between T-cell antigen receptor (TCR) stimulation and T-cell effector functions, providing a structural basis for T-cell morphological changes and signal transduction. Accumulating evidence positions the Wiskott-Aldrich syndrome protein (WASp), a scaffolding protein that promotes actin polymerization, at the center of actin cytoskeleton-dependent T-cell function. During the past decade, we and others have utilized multidisciplinary technologies, including live-cell imaging, biochemical, and biophysical analyses, to gain insight into the mechanisms by which WASp and other cytoskeletal proteins control actin homeostasis. Following TCR engagement, WASp is rapidly activated and recruited to TCR microclusters, as part of multiprotein complexes, where it promotes actin remodeling. Late in the activation process, WASp is internalized and eventually degraded. In this review, we describe the dynamic interactions of WASp with signaling proteins, which regulate its activation and recruitment to the TCR and to actin-rich sites. Finally, we present the molecular mechanism of WASp downregulation. Some of the signaling proteins that mediate WASp activation eventually lead to its degradation. Thus, we focus here on the regulation of WASp expression and function and the mechanisms whereby they control actin machinery and T-cell effector functions.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Omri
authors.initials: O
authors.lastname: Matalon
authors.forename: Barak
authors.initials: B
authors.lastname: Reicher
authors.forename: Mira
authors.initials: M
authors.lastname: Barda-Saad
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D006706:Homeostasis; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000199:Actins; D051316:Wiskott-Aldrich Syndrome Protein
keywords: TCR; WASp; actin polymerization; cytoskeleton; lymphocyte; signaling