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

Nordenfelt, Pontus LU ; Elliott, Hunter L. and Springer, Timothy A. (2016) In Nature Communications 7.
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
7
publisher
Nature Publishing Group
external identifiers
  • scopus:84991018173
  • wos:000385549500001
ISSN
2041-1723
DOI
10.1038/ncomms13119
language
English
LU publication?
yes
id
a342514e-7869-4104-b504-99d0e53c648c
date added to LUP
2016-11-01 08:27:19
date last changed
2017-11-19 04:34:25
@article{a342514e-7869-4104-b504-99d0e53c648c,
  abstract     = {<p>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.</p>},
  articleno    = {13119},
  author       = {Nordenfelt, Pontus and Elliott, Hunter L. and Springer, Timothy A.},
  issn         = {2041-1723},
  language     = {eng},
  month        = {10},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Coordinated integrin activation by actin-dependent force during T-cell migration},
  url          = {http://dx.doi.org/10.1038/ncomms13119},
  volume       = {7},
  year         = {2016},
}