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Nat Commun. 2017 Dec 11;8(1):2047. doi: 10.1038/s41467-017-01848-y.

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

Author information

1
Whitman Center, Marine Biological Laboratory, Woods Hole, MA, 02543, USA.
2
Physiology Course, Marine Biological Laboratory, Woods Hole, MA, 02543, USA.
3
Program in Cellular and Molecular Medicine, Children's Hospital, and Department of Biological Chemistry and Molecular Pharmacology and Medicine, Harvard Medical School, Boston, MA, 02115, USA.
4
Division of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, 221 84, Sweden.
5
Eugene Bell Center, Marine Biological Laboratory, Woods Hole, MA, 02543, USA.
6
Chan Zuckerberg Biohub, San Francisco, CA, 94158, USA.
7
National Center for Biological Sciences, Bangalore, 560065, India.
8
Cell Biology and Physiology Center, NHLBI, NIH, Bethesda, MD, 20824, USA.
9
Howard Hughes Medical Institute, University of Washington, Seattle, WA, 98195, USA.
10
Institute for Molecular Science, Myodaiji, Okazaki, 444-8585, Japan.
11
Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.
12
Whitman Center, Marine Biological Laboratory, Woods Hole, MA, 02543, USA. springer_lab@crystal.harvard.edu.
13
Physiology Course, Marine Biological Laboratory, Woods Hole, MA, 02543, USA. springer_lab@crystal.harvard.edu.
14
Program in Cellular and Molecular Medicine, Children's Hospital, and Department of Biological Chemistry and Molecular Pharmacology and Medicine, Harvard Medical School, Boston, MA, 02115, USA. springer_lab@crystal.harvard.edu.

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.

PMID:
29229906
PMCID:
PMC5725580
DOI:
10.1038/s41467-017-01848-y
[Indexed for MEDLINE]
Free PMC Article

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