
@article {25251,
	title = {Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {114},
	year = {2017},
	month = {2017 Oct 03},
	pages = {10648-10653},
	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>
},
	issn = {1091-6490},
	doi = {10.1073/pnas.1701136114},
	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}
}
