TitleActin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions.
Publication TypeJournal Article
Year of Publication2017
AuthorsSwaminathan V, Kalappurakkal JMathew, Mehta SB, Nordenfelt P, Moore TI, Koga N, Baker DA, Oldenbourg R, Tani T, Mayor S, Springer TA, Waterman CM
JournalProc Natl Acad Sci U S A
Date Published2017 Oct 03

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID29073038
PubMed Central IDPMC5635867