Cofilin

• Verfasst von: Samstag, Yvonne [VerfasserIn]
• Verfasst von: John, Isabel [VerfasserIn]
• Verfasst von: Wabnitz, Guido H. [VerfasserIn]
• Titel: Cofilin
• Titelzusatz: a redox sensitive mediator of actin dynamics during T-cell activation and migration
• Verf.angabe: Yvonne Samstag, Isabel John, Guido H. Wabnitz
• E-Jahr: 2013
• Jahr: 10 October 2013
• Umfang: 18 S.
• Teil: volume:256
• Teil: year:2013
• Teil: number:1
• Teil: pages:30-47
• Teil: extent:18
• Fussnoten: Gesehen am 25.06.2021
• Titel Quelle: Enthalten in: Immunological reviews
• Ort Quelle: Oxford : Wiley-Blackwell, 1969
• Jahr Quelle: 2013
• Band/Heft Quelle: 256(2013), 1, Seite 30-47
• ISSN Quelle: 1600-065X
• DOI: doi:10.1111/imr.12115
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: actin cytoskeleton
• Sach-SW: Actin Depolymerizing Factors
• Sach-SW: Actins
• Sach-SW: Animals
• Sach-SW: Cell Membrane
• Sach-SW: Cell Movement
• Sach-SW: Chemokines
• Sach-SW: costimulation
• Sach-SW: Humans
• Sach-SW: immune synapse
• Sach-SW: Immunity, Cellular
• Sach-SW: Lymphocyte Activation
• Sach-SW: microenvironment
• Sach-SW: Oxidation-Reduction
• Sach-SW: Phospholipids
• Sach-SW: redox
• Sach-SW: T-cell activation
• Sach-SW: T-Lymphocyte Subsets
• K10plus-PPN: 1761299468

Abstract

Cofilin is an actin-binding protein that depolymerizes and/or severs actin filaments. This dual function of cofilin makes it one of the major regulators of actin dynamics important for T-cell activation and migration. The activity of cofilin is spatio-temporally regulated. Its main control mechanisms comprise a molecular toolbox of phospho-, phospholipid, and redox regulation. Phosphorylated cofilin is inactive and represents the dominant cofilin fraction in the cytoplasm of resting human T cells. A fraction of dephosphorylated cofilin is kept inactive at the plasma membrane by binding to phosphatidylinositol 4,5-bisphosphate. Costimulation via the T-cell receptor/CD3 complex (signal 1) together with accessory receptors (signal 2) or triggering through the chemokine SDF1α (stromal cell-derived factor 1α) induce Ras-dependent dephosphorylation of cofilin, which is important for immune synapse formation, T-cell activation, and T-cell migration. Recently, it became evident that cofilin is also highly sensitive for microenvironmental changes, particularly for alterations in the redox milieu. Cofilin is inactivated by oxidation, provoking T-cell hyporesponsiveness or necrotic-like programmed cell death. In contrast, in a reducing environment, even phosphatidylinositol 4,5-bisphosphate-bound cofilin becomes active, leading to actin dynamics in the vicinity of the plasma membrane. In addition to the well-established three signals for T-cell activation, this microenvironmental control of cofilin delivers a modulating signal for T-cell-dependent immune reactions. This fourth modulating signal highly impacts both initial T-cell activation and the effector phase of T-cell-mediated immune responses.