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Calcium bursts allow rapid reorganization of EFhD2/Swip-1 cross-linked actin networks in epithelial wound closure

Author

Listed:
  • Franziska Lehne

    (Philipps-University Marburg)

  • Thomas Pokrant

    (Hannover Medical School)

  • Sabnam Parbin

    (University Medical Center Göttingen)

  • Gabriela Salinas

    (University Medical Center Göttingen)

  • Jörg Großhans

    (Philipps-University Marburg)

  • Katja Rust

    (Philipps-University Marburg)

  • Jan Faix

    (Hannover Medical School)

  • Sven Bogdan

    (Philipps-University Marburg)

Abstract

Changes in cell morphology require the dynamic remodeling of the actin cytoskeleton. Calcium fluxes have been suggested as an important signal to rapidly relay information to the actin cytoskeleton, but the underlying mechanisms remain poorly understood. Here, we identify the EF-hand domain containing protein EFhD2/Swip-1 as a conserved lamellipodial protein strongly upregulated in Drosophila macrophages at the onset of metamorphosis when macrophage behavior shifts from quiescent to migratory state. Loss- and gain-of-function analysis confirm a critical function of EFhD2/Swip-1 in lamellipodial cell migration in fly and mouse melanoma cells. Contrary to previous assumptions, TIRF-analyses unambiguously demonstrate that EFhD2/Swip-1 proteins efficiently cross-link actin filaments in a calcium-dependent manner. Using a single-cell wounding model, we show that EFhD2/Swip-1 promotes wound closure in a calcium-dependent manner. Mechanistically, our data suggest that transient calcium bursts reduce EFhD2/Swip-1 cross-linking activity and thereby promote rapid reorganization of existing actin networks to drive epithelial wound closure.

Suggested Citation

  • Franziska Lehne & Thomas Pokrant & Sabnam Parbin & Gabriela Salinas & Jörg Großhans & Katja Rust & Jan Faix & Sven Bogdan, 2022. "Calcium bursts allow rapid reorganization of EFhD2/Swip-1 cross-linked actin networks in epithelial wound closure," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30167-0
    DOI: 10.1038/s41467-022-30167-0
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    1. Jiacheng Wu & Xiaoqing Xu & Jiaqi Duan & Yangyang Chai & Jiaying Song & Dongsheng Gong & Bingjing Wang & Ye Hu & Taotao Han & Yuanyuan Ding & Yin Liu & Jingnan Li & Xuetao Cao, 2024. "EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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