Oxidation of cofilin mediates T cell hyporesponsiveness under oxidative stress conditions
Oxidative stress leads to impaired T cell activation. A central integrator of T cell activation is the actin-remodelling protein cofilin. Cofilin is activated through dephosphorylation at Ser3. Activated cofilin enables actin dynamics through severing and depolymerization of F-actin. Binding of cofi...
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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
4 September 2008
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| In: |
Immunity
Year: 2008, Jahrgang: 29, Heft: 3, Pages: 404-413 |
| ISSN: | 1097-4180 |
| DOI: | 10.1016/j.immuni.2008.06.016 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.immuni.2008.06.016 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1074761308003695 
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| Verfasserangaben: | Martin Klemke, Guido H. Wabnitz, Faustina Funke, Beate Funk, Henning Kirchgessner, Yvonne Samstag |
| Zusammenfassung: | Oxidative stress leads to impaired T cell activation. A central integrator of T cell activation is the actin-remodelling protein cofilin. Cofilin is activated through dephosphorylation at Ser3. Activated cofilin enables actin dynamics through severing and depolymerization of F-actin. Binding of cofilin to actin is required for formation of the immune synapse and T cell activation. Here, we showed that oxidatively stressed human T cells were impaired in chemotaxis- and costimulation-induced F-actin modulation. Although cofilin was dephosphorylated, steady-state F-actin levels increased under oxidative stress conditions. Mass spectrometry revealed that cofilin itself was a target for oxidation. Cofilin oxidation induced formation of an intramolecular disulfide bridge and loss of its Ser3 phosphorylation. Importantly, dephosphorylated oxidized cofilin, although still able to bind to F-actin, did not mediate F-actin depolymerization. Impairing actin dynamics through oxidation of cofilin provides a molecular explanation for the T cell hyporesponsiveness caused by oxidative stress. |
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| Beschreibung: | Gesehen am 16.07.2021 |
| Beschreibung: | Online Resource |
| ISSN: | 1097-4180 |
| DOI: | 10.1016/j.immuni.2008.06.016 |