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

by Baker, David A. , Kalappurakkal, Joseph Mathew , Mehta, Shalin B. , Tani, Tomomi , Oldenbourg, Rudolf , Springer, Timothy A. , Waterman, Clare M. , Swaminathan, Vinay , Mayor, Satyajit , Nordenfelt, Pontus , Koga, Nobuyasu , Moore, Travis I.

in Actin / Actins - genetics / Actins - metabolism / Activation / Animals / Binding / Binding sites / Biologi / Biological Sciences / Biophysics and Computational Biology / Cell adhesion / Cell adhesion & migration / Cell Biology / Cell Line / Cell migration / Cell Movement - physiology / Cellbiologi / Contractility / Cues / Cytoskeleton / Cytoskeleton - genetics / Cytoskeleton - metabolism / Embryo, Mammalian - cytology / Embryo, Mammalian - metabolism / Fibroblasts / Fibroblasts - cytology / Fibroblasts - metabolism / Fluorescence / Fluorescence microscopy / Focal Adhesions - genetics / Focal Adhesions - metabolism / Integrin alphaVbeta3 - genetics / Integrin alphaVbeta3 - metabolism / Integrins / Ligands / Mice / Microscopy / Natural Sciences / Naturvetenskap / Polymerization / Proteins / Receptors / Talin

2017

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

2017

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

2017

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Journal Article

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

Baker, David A.,

Kalappurakkal, Joseph Mathew,

Mehta, Shalin B.,

Tani, Tomomi,

Oldenbourg, Rudolf,

Springer, Timothy A.,

Waterman, Clare M.,

Swaminathan, Vinay,

Mayor, Satyajit,

Nordenfelt, Pontus,

Koga, Nobuyasu,

Moore, Travis I.

2017

Overview

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.

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Publisher

National Academy of Sciences

Subject

Actin

/ Actins - genetics

/ Actins - metabolism

/ Activation

/ Animals

/ Binding

/ Binding sites