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Coordinated integrin activation by actin-dependent force during T-cell migration

Author

Listed:
  • Pontus Nordenfelt

    (Harvard Medical School and Program in Cellular and Molecular Medicine, Children’s Hospital Boston
    Image and Data Analysis Core, Harvard Medical School
    Faculty of Medicine, Lund University)

  • Hunter L. Elliott

    (Image and Data Analysis Core, Harvard Medical School)

  • Timothy A. Springer

    (Harvard Medical School and Program in Cellular and Molecular Medicine, Children’s Hospital Boston)

Abstract

For a cell to move forward it must convert chemical energy into mechanical propulsion. Force produced by actin polymerization can generate traction across the plasma membrane by transmission through integrins to their ligands. However, the role this force plays in integrin activation is unknown. Here we show that integrin activity and cytoskeletal dynamics are reciprocally linked, where actin-dependent force itself appears to regulate integrin activity. We generated fluorescent tension-sensing constructs of integrin αLβ2 (LFA-1) to visualize intramolecular tension during cell migration. Using quantitative imaging of migrating T cells, we correlate tension in the αL or β2 subunit with cell and actin dynamics. We find that actin engagement produces tension within the β2 subunit to induce and stabilize an active integrin conformational state and that this requires intact talin and kindlin motifs. This supports a general mechanism where localized actin polymerization can coordinate activation of the complex machinery required for cell migration.

Suggested Citation

  • Pontus Nordenfelt & Hunter L. Elliott & Timothy A. Springer, 2016. "Coordinated integrin activation by actin-dependent force during T-cell migration," Nature Communications, Nature, vol. 7(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13119
    DOI: 10.1038/ncomms13119
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    Cited by:

    1. Arventh Velusamy & Radhika Sharma & Sk Aysha Rashid & Hiroaki Ogasawara & Khalid Salaita, 2024. "DNA mechanocapsules for programmable piconewton responsive drug delivery," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Tianchi Chen & Cecilia H. Fernández-Espartero & Abigail Illand & Ching-Ting Tsai & Yang Yang & Benjamin Klapholz & Pierre Jouchet & Mélanie Fabre & Olivier Rossier & Bianxiao Cui & Sandrine Lévêque-Fo, 2024. "Actin-driven nanotopography promotes stable integrin adhesion formation in developing tissue," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Markus Haake & Beatrice Haack & Tina Schäfer & Patrick N. Harter & Greta Mattavelli & Patrick Eiring & Neha Vashist & Florian Wedekink & Sabrina Genssler & Birgitt Fischer & Julia Dahlhoff & Fatemeh M, 2023. "Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Myung Hyun Jo & Jing Li & Valentin Jaumouillé & Yuxin Hao & Jessica Coppola & Jiabin Yan & Clare M. Waterman & Timothy A. Springer & Taekjip Ha, 2022. "Single-molecule characterization of subtype-specific β1 integrin mechanics," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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