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Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions

Swaminathan, Vinay; Kalappurakkal, Joseph Mathew; Mehta, Shalin B.; Nordenfelt, Pontus LU ; Moore, Travis I.; Koga, Nobuyasu; Baker, David A.; Oldenbourg, Rudolf; Tani, Tomomi and Mayor, Satyajit, et al. (2017) In Proceedings of the National Academy of Sciences of the United States of America 114(40). p.10648-10653
Abstract

Integrins are transmembrane receptors that, upon activation, bind extracellular ligands and link them to the actin filament (F-actin) cytoskeleton to mediate cell adhesion and migration. Cytoskeletal forces in migrating cells generated by polymerization- or contractility-driven “retrograde flow” of F-actin from the cell leading edge have been hypothesized to mediate integrin activation for ligand binding. This predicts that these forces should align and orient activated, ligand-bound integrins at the leading edge. Here, polarization-sensitive fluorescence microscopy of GFP-αVβ3 integrins in fibroblasts shows that integrins are coaligned in a specific orientation within focal adhesions (FAs) in a manner dependent on binding immobilized... (More)

Integrins are transmembrane receptors that, upon activation, bind extracellular ligands and link them to the actin filament (F-actin) cytoskeleton to mediate cell adhesion and migration. Cytoskeletal forces in migrating cells generated by polymerization- or contractility-driven “retrograde flow” of F-actin from the cell leading edge have been hypothesized to mediate integrin activation for ligand binding. This predicts that these forces should align and orient activated, ligand-bound integrins at the leading edge. Here, polarization-sensitive fluorescence microscopy of GFP-αVβ3 integrins in fibroblasts shows that integrins are coaligned in a specific orientation within focal adhesions (FAs) in a manner dependent on binding immobilized ligand and a talin-mediated linkage to the F-actin cytoskeleton. These findings, together with Rosetta modeling, suggest that integrins in FA are coaligned and may be highly tilted by cytoskeletal forces. Thus, the F-actin cytoskeleton sculpts an anisotropic molecular scaffold in FAs, and this feature may underlie the ability of migrating cells to sense directional extracellular cues.

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publication status
published
subject
keywords
Cell migration, Fluorescence polarization microscopy, Mechanosensing
in
Proceedings of the National Academy of Sciences of the United States of America
volume
114
issue
40
pages
6 pages
publisher
National Acad Sciences
external identifiers
  • scopus:85030235451
  • wos:000412130500058
ISSN
0027-8424
DOI
10.1073/pnas.1701136114
language
English
LU publication?
yes
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a6fe995c-14fb-477f-91b1-d615262bebc3
date added to LUP
2017-11-28 08:40:23
date last changed
2018-01-16 13:26:35
@article{a6fe995c-14fb-477f-91b1-d615262bebc3,
  abstract     = {<p>Integrins are transmembrane receptors that, upon activation, bind extracellular ligands and link them to the actin filament (F-actin) cytoskeleton to mediate cell adhesion and migration. Cytoskeletal forces in migrating cells generated by polymerization- or contractility-driven “retrograde flow” of F-actin from the cell leading edge have been hypothesized to mediate integrin activation for ligand binding. This predicts that these forces should align and orient activated, ligand-bound integrins at the leading edge. Here, polarization-sensitive fluorescence microscopy of GFP-αVβ3 integrins in fibroblasts shows that integrins are coaligned in a specific orientation within focal adhesions (FAs) in a manner dependent on binding immobilized ligand and a talin-mediated linkage to the F-actin cytoskeleton. These findings, together with Rosetta modeling, suggest that integrins in FA are coaligned and may be highly tilted by cytoskeletal forces. Thus, the F-actin cytoskeleton sculpts an anisotropic molecular scaffold in FAs, and this feature may underlie the ability of migrating cells to sense directional extracellular cues.</p>},
  author       = {Swaminathan, Vinay and Kalappurakkal, Joseph Mathew and Mehta, Shalin B. and Nordenfelt, Pontus and Moore, Travis I. and Koga, Nobuyasu and Baker, David A. and Oldenbourg, Rudolf and Tani, Tomomi and Mayor, Satyajit and Springer, Timothy A. and Waterman, Clare M.},
  issn         = {0027-8424},
  keyword      = {Cell migration,Fluorescence polarization microscopy,Mechanosensing},
  language     = {eng},
  month        = {10},
  number       = {40},
  pages        = {10648--10653},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions},
  url          = {http://dx.doi.org/10.1073/pnas.1701136114},
  volume       = {114},
  year         = {2017},
}