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

Swaminathan, VinayNational Heart Lung and Blood Institute,Marine Biological Laboratory (author)

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.

Kalappurakkal, Joseph MathewNational Centre for Biological Sciences,Marine Biological Laboratory (author)
Mehta, Shalin B.Marine Biological Laboratory (author)
Nordenfelt, PontusLund University,Lunds universitet,epIgG,Forskargrupper vid Lunds universitet,Lund University Research Groups,Harvard University,Boston Children's Hospital,Marine Biological Laboratory(Swepub:lu)med-pnl (author)
Moore, Travis I.Boston Children's Hospital,Harvard University,Marine Biological Laboratory (author)
Koga, NobuyasuInstitute for Molecular Science,University of Washington (author)
Baker, David A.University of Washington (author)
Oldenbourg, RudolfMarine Biological Laboratory (author)
Tani, TomomiMarine Biological Laboratory (author)
Mayor, SatyajitMarine Biological Laboratory,National Centre for Biological Sciences (author)
Springer, Timothy A.Marine Biological Laboratory,Boston Children's Hospital,Harvard University (author)
Waterman, Clare M.Marine Biological Laboratory,National Heart Lung and Blood Institute (author)
National Heart Lung and Blood InstituteMarine Biological Laboratory (creator_code:org_t)

In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences114:40, s. 10648-106530027-8424
In:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences114:40, s. 10648-106531091-6490

By the author/editor: Swaminathan, Vin ...; Kalappurakkal, J ...; Mehta, Shalin B.; Nordenfelt, Pont ...; Moore, Travis I.; Koga, Nobuyasu; show more...; Baker, David A.; Oldenbourg, Rudo ...; Tani, Tomomi; Mayor, Satyajit; Springer, Timoth ...; Waterman, Clare ...; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Cell Biology

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