ArticleThe Journal of biological chemistry2013
A reducing milieu renders cofilin insensitive to phosphatidylinositol 4,5-bisphosphate (PIP2) inhibition.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- The Actin Regulators Involved in the Function and Related Diseases of Lymphocytes.Frontiers in immunology · 2022Review
- Redox Regulation of the Actin Cytoskeleton in Cell Migration and Adhesion: On the Way to a Spatiotemporal View.Frontiers in cell and developmental biology · 2020Review
- Cofilin and profilin: partners in cancer aggressiveness.Biophysical reviews · 2018Review
- The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development.PLoS biology · 2018Article
- Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione.Frontiers in immunology · 2018Article
- Cofilin-mediated Neuronal Apoptosis via p53 Translocation and PLD1 Regulation.Scientific reports · 2017Article
- The pro-oxidative drug WF-10 inhibits serial killing by primary human cytotoxic T-cells.Cell death discovery · 2016Article
- Ultrasensitivity in the Cofilin Signaling Module: A Mechanism for Tuning T Cell Responses.Frontiers in immunology · 2016Review
- Polarized cell motility induces hydrogen peroxide to inhibit cofilin via cysteine oxidation.Current biology : CB · 2015Article
- S-nitrosylation of cofilin-1 mediates estradiol-17β-stimulated endothelial cytoskeleton remodeling.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Cofilin: a redox sensitive mediator of actin dynamics during T-cell activation and migration.Immunological reviews · 2013Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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