A specific role for endothelial EPLIN-isoform-regulated actin dynamics in neutrophil transmigration
Proinflammatory cytokines such as TNF-α or IL-1β activate the endothelium promoting leukocyte transendothelial migration (TEM) via expression of cell adhesion molecules (CAM) and cause actin remodelling. However, the function of endothelial actin remodelling in TEM remains elusive, despite its involvement in the formation of docking structures, diapedesis pores and pore resealing. Here, we establish EPLIN-isoforms, EPLIN-β and EPLIN-α, as differential regulators of TNF-α-inducedactin-remodelling significantly affecting TEM. We find EPLIN-β-induced stress fiber formation upon TNF-α-treatment weakens endothelial junctions, upregulates junctional dynamics and facilitates intercellular gaps for TEM. Increased junctional dynamics involves branched actin filaments under the control of EPLIN-α, including docking structure formation and transmigratory pore closure. We further establish by EPLIN deletion and re-expression studies that EPLIN-α-mediated termination of branched actin filaments maintains TNF-α-induced junctional dynamics and intercellular gaps facilitating TEM. These findings highlight the critical role of TNF-α-induced differential actin dynamics, controlled by EPLIN isoforms, in TEM. These results also offer a wider understanding of inflammation-induced TEM by incorporating altered junctional dynamics alongside upregulation of cell adhesion molecules.
Authors
- M. Giglmaier (ORCID: https://orcid.org/0000-0003-3754-9219)
- Parisa Ghanbari (ORCID: https://orcid.org/0000-0002-7432-2147)
- S. Currie (ORCID: https://orcid.org/0000-0002-2190-7096)
- Dietmar Vestweber (ORCID: https://orcid.org/0000-0002-3517-732X)
- Klemens Rottner (ORCID: https://orcid.org/0000-0003-4244-4198)
- Sigrid März (ORCID: https://orcid.org/0000-0001-6836-7755)
- Maria Odenthal-Schnittler (ORCID: https://orcid.org/0000-0001-8467-7585)
- Hans‐Joachim Schnittler (ORCID: https://orcid.org/0000-0001-6807-3343)
- Magdalena Miętkowska
- Jan Philip Kipcke
- Hermann Schillers (ORCID: https://orcid.org/0000-0001-6090-4771)
- Muna Taha (ORCID: https://orcid.org/0000-0003-2674-6399)
- Erez Raz (ORCID: https://orcid.org/0000-0002-6347-3302)
- Anja Blanqué
- Jonas Franz (ORCID: https://orcid.org/0000-0001-7523-6622)
- Julian Wegner
- Mohammed Aldirawi
Institutions
- University of Münster (DE)
- Robert Koch Institute (DE)
- Helmholtz Centre for Infection Research (DE)
- Max Planck Institute for Molecular Biomedicine (DE)
- Institute of Molecular Biology (DE)
- Technical University of Munich (DE)
- Technische Universität Braunschweig (DE)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-05-05
- DOI
- https://doi.org/10.1038/s41598-025-98192-9
- Citations
- 3
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 3.45
Funders
- International Max Planck Research School for Environmental, Cellular and Molecular Microbiology
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Max-Planck-Gesellschaft
- Westfälische Wilhelms-Universität Münster