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Author Spotlight: Understanding Disease Mechanisms Through Real-Time Analysis of T-Cell Migration
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Coordinated integrin activation by actin-dependent force during T-cell migration.

Pontus Nordenfelt1,2,3, Hunter L Elliott2, Timothy A Springer1

  • 1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Program in Cellular and Molecular Medicine, Children's Hospital Boston, 3 Blackfan Circle, Boston, Massachusetts 02115, USA.

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|October 11, 2016
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Summary
This summary is machine-generated.

Cell migration relies on converting chemical energy into mechanical force. This study reveals that actin-generated force directly regulates integrin activation, a key step in cell movement.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Molecular Biology

Background:

  • Cellular locomotion requires converting chemical energy into mechanical propulsion.
  • Actin polymerization generates force for cell migration via integrins, but its role in integrin activation is unclear.

Purpose of the Study:

  • To investigate the role of actin-dependent force in integrin activation during cell migration.
  • To visualize intramolecular tension within integrins during T cell migration.

Main Methods:

  • Generated fluorescent tension-sensing constructs of integrin αLβ2 (LFA-1).
  • Utilized quantitative imaging of migrating T cells to correlate integrin subunit tension with cell and actin dynamics.

Main Results:

  • Actin engagement generates tension within the β2 subunit of LFA-1.
  • This tension induces and stabilizes an active integrin conformation.
  • The observed effect requires intact talin and kindlin binding motifs.

Conclusions:

  • Integrin activity and cytoskeletal dynamics are reciprocally linked.
  • Actin-dependent force plays a regulatory role in integrin activation.
  • Localized actin polymerization can coordinate the machinery essential for cell migration.