| Online-Ressource |
Verfasst von: | Schulte, Bianca [VerfasserIn]  |
| John, Isabel [VerfasserIn]  |
| Simon, Bernd [VerfasserIn]  |
| Brockmann, Christoph [VerfasserIn]  |
| Oelmeier, Stefan A. [VerfasserIn]  |
| Jahraus, Beate [VerfasserIn]  |
| Kirchgessner, Henning [VerfasserIn]  |
| Riplinger, Selina [VerfasserIn]  |
| Carlomagno, Teresa [VerfasserIn]  |
| Wabnitz, Guido H. [VerfasserIn]  |
| Samstag, Yvonne [VerfasserIn]  |
Titel: | A reducing milieu renders cofilin insensitive to phosphatidylinositol 4,5-bisphosphate (PIP2) inhibition |
Verf.angabe: | Bianca Schulte, Isabel John, Bernd Simon, Christoph Brockmann, Stefan A. Oelmeier, Beate Jahraus, Henning Kirchgessner, Selina Riplinger, Teresa Carlomagno, Guido H. Wabnitz and Yvonne Samstag |
Jahr: | 2013 |
Umfang: | 10 S. |
Teil: | volume:288 |
| year:2013 |
| number:41 |
| pages:29430-29439 |
| extent:10 |
Fussnoten: | Gesehen am 28.06.2021 |
Titel Quelle: | Enthalten in: The journal of biological chemistry |
Ort Quelle: | Bethesda, Md. : ASBMB Publications, 1905 |
Jahr Quelle: | 2013 |
Band/Heft Quelle: | 288(2013), 41, Seite 29430-29439 |
ISSN Quelle: | 1083-351X |
Abstract: | Oxidative stress can lead to T cell hyporesponsiveness. A reducing micromilieu (e.g. provided by dendritic cells) can rescue T cells from such oxidant-induced dysfunction. However, the reducing effects on proteins leading to restored T cell activation remained unknown. One key molecule of T cell activation is the actin-remodeling protein cofilin, which is dephosphorylated on serine 3 upon T cell costimulation and has an essential role in formation of mature immune synapses between T cells and antigen-presenting cells. Cofilin is spatiotemporally regulated; at the plasma membrane, it can be inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2). Here, we show by NMR spectroscopy that a reducing milieu led to structural changes in the cofilin molecule predominantly located on the protein surface. They overlapped with the PIP2- but not actin-binding sites. Accordingly, reduction of cofilin had no effect on F-actin binding and depolymerization and did not influence the cofilin phosphorylation state. However, it did prevent inhibition of cofilin activity through PIP2. Therefore, a reducing milieu may generate an additional pool of active cofilin at the plasma membrane. Consistently, in-flow microscopy revealed increased actin dynamics in the immune synapse of untransformed human T cells under reducing conditions. Altogether, we introduce a novel mechanism of redox regulation: reduction of the actin-remodeling protein cofilin renders it insensitive to PIP2 inhibition, resulting in enhanced actin dynamics. |
DOI: | doi:10.1074/jbc.M113.479766 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1074/jbc.M113.479766 |
| Volltext: https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)48764-2 |
| DOI: https://doi.org/10.1074/jbc.M113.479766 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Actin Depolymerizing Factors |
| Actins |
| Blotting, Western |
| Cell Line, Tumor |
| Cell Membrane |
| Cells, Cultured |
| Cofilin |
| Cysteine |
| Humans |
| Magnetic Resonance Spectroscopy |
| Models, Molecular |
| Molecular Dynamics Simulation |
| Mutation |
| Oxidation-Reduction |
| Phosphatidylinositol 4,5-Diphosphate |
| Phosphatidylinositol Signaling |
| Phosphorylation |
| Polymerization |
| Protein Binding |
| Protein Conformation |
| Protein Structure, Tertiary |
| Redox Regulation |
| T Cell |
| T-Lymphocytes |
K10plus-PPN: | 1761321447 |
Verknüpfungen: | → Zeitschrift |
¬A¬ reducing milieu renders cofilin insensitive to phosphatidylinositol 4,5-bisphosphate (PIP2) inhibition / Schulte, Bianca [VerfasserIn]; 2013 (Online-Ressource)