Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions
Swaminathan, Vinay LU ; 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.
(Less)
- author
- Swaminathan, Vinay
LU
; 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. (More)
- Swaminathan, Vinay
LU
; Kalappurakkal, Joseph Mathew
; Mehta, Shalin B.
; Nordenfelt, Pontus
LU
; Moore, Travis I.
; Koga, Nobuyasu
; Baker, David A.
; Oldenbourg, Rudolf
; Tani, Tomomi
; Mayor, Satyajit
; Springer, Timothy A.
and Waterman, Clare M.
(Less)
- organization
- publishing date
- 2017-10-03
- type
- Contribution to journal
- 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 Academy of Sciences
- external identifiers
-
- scopus:85030235451
- pmid:29073038
- wos:000412130500058
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.1701136114
- language
- English
- LU publication?
- yes
- id
- a6fe995c-14fb-477f-91b1-d615262bebc3
- date added to LUP
- 2017-11-28 08:40:23
- date last changed
- 2024-07-08 05:59:40
@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}},
keywords = {{Cell migration; Fluorescence polarization microscopy; Mechanosensing}},
language = {{eng}},
month = {{10}},
number = {{40}},
pages = {{10648--10653}},
publisher = {{National Academy of 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}},
doi = {{10.1073/pnas.1701136114}},
volume = {{114}},
year = {{2017}},
}