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

Nordenfelt, Pontus LU ; Moore, Travis I; Mehta, Shalin B; Kalappurakkal, Joseph Mathew; Swaminathan, Vinay LU ; Koga, Nobuyasu; Lambert, Talley J; Baker, David; Waters, Jennifer C and Oldenbourg, Rudolf, et al. (2017) In Nature Communications 8(1).
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... (More)

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.

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Nature Communications
volume
8
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85042053308
ISSN
2041-1723
DOI
10.1038/s41467-017-01848-y
language
English
LU publication?
yes
id
cd56e4fd-969a-41d0-8ae1-266cd7770694
date added to LUP
2018-01-18 07:25:04
date last changed
2019-09-17 04:23:58
@article{cd56e4fd-969a-41d0-8ae1-266cd7770694,
  abstract     = {<p>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.</p>},
  articleno    = {2047},
  author       = {Nordenfelt, Pontus and Moore, Travis I and Mehta, Shalin B and Kalappurakkal, Joseph Mathew and Swaminathan, Vinay and Koga, Nobuyasu and Lambert, Talley J and Baker, David and Waters, Jennifer C and Oldenbourg, Rudolf and Tani, Tomomi and Mayor, Satyajit and Waterman, Clare M and Springer, Timothy A},
  issn         = {2041-1723},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration},
  url          = {http://dx.doi.org/10.1038/s41467-017-01848-y},
  volume       = {8},
  year         = {2017},
}