Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration

Pontus Nordenfelt, Travis I. Moore, Shalin B. Mehta, Joseph Mathew Kalappurakkal, Vinay Swaminathan, Nobuyasu Koga, Talley J. Lambert, David Baker, Jennifer C. Waters, Rudolf Oldenbourg, Tomomi Tani, Satyajit Mayor, Clare M. Waterman and Timothy A. Springer ()
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Pontus Nordenfelt: Marine Biological Laboratory
Travis I. Moore: Marine Biological Laboratory
Shalin B. Mehta: Marine Biological Laboratory
Joseph Mathew Kalappurakkal: Marine Biological Laboratory
Vinay Swaminathan: Marine Biological Laboratory
Nobuyasu Koga: University of Washington
Talley J. Lambert: Harvard Medical School
David Baker: University of Washington
Jennifer C. Waters: Harvard Medical School
Rudolf Oldenbourg: Marine Biological Laboratory
Tomomi Tani: Marine Biological Laboratory
Satyajit Mayor: Marine Biological Laboratory
Clare M. Waterman: Marine Biological Laboratory
Timothy A. Springer: Marine Biological Laboratory

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: Abstract Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here, we test whether the integrin, when engaged to an extracellular ligand and the cytoskeleton, adopts a specific orientation dictated by the direction of actin flow on the surface of migrating cells. We insert GFP into the rigid, ligand-binding head of the integrin, model with Rosetta the orientation of GFP and its transition dipole relative to the integrin head, and measure orientation with fluorescence polarization microscopy. Cytoskeleton and ligand-bound integrins orient in the same direction as retrograde actin flow with their cytoskeleton-binding β-subunits tilted by applied force. The measurements demonstrate that intracellular forces can orient cell surface integrins and support a molecular model of integrin activation by cytoskeletal force. Our results place atomic, Å-scale structures of cell surface receptors in the context of functional and cellular, μm-scale measurements.

Date: 2017
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DOI: 10.1038/s41467-017-01848-y

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