Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions.
|Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions.
|Year of Publication
|Swaminathan V, Kalappurakkal JMathew, Mehta SB, Nordenfelt P, Moore TI, Koga N, Baker DA, Oldenbourg R, Tani T, Mayor S, Springer TA, Waterman CM
|Proc Natl Acad Sci U S A
|2017 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.
|Proc. Natl. Acad. Sci. U.S.A.
|PubMed Central ID