Cofilin: a redox sensitive mediator of actin dynamics during T-cell activation and migration
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 mechanism...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
10 October 2013
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| In: |
Immunological reviews
Year: 2013, Volume: 256, Issue: 1, Pages: 30-47 |
| ISSN: | 1600-065X |
| DOI: | 10.1111/imr.12115 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/imr.12115 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/10.1111/imr.12115 
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| Author Notes: | Yvonne Samstag, Isabel John, Guido H. Wabnitz |
MARC
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| 520 | |a 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. | ||
| 650 | 4 | |a actin cytoskeleton | |
| 650 | 4 | |a Actin Depolymerizing Factors | |
| 650 | 4 | |a Actins | |
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Cell Membrane | |
| 650 | 4 | |a Cell Movement | |
| 650 | 4 | |a Chemokines | |
| 650 | 4 | |a costimulation | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a immune synapse | |
| 650 | 4 | |a Immunity, Cellular | |
| 650 | 4 | |a Lymphocyte Activation | |
| 650 | 4 | |a microenvironment | |
| 650 | 4 | |a Oxidation-Reduction | |
| 650 | 4 | |a Phospholipids | |
| 650 | 4 | |a redox | |
| 650 | 4 | |a T-cell activation | |
| 650 | 4 | |a T-Lymphocyte Subsets | |
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