TitleDirection of actin flow dictates integrin LFA-1 orientation during leukocyte migration.
Publication TypeJournal Article
Year of Publication2017
AuthorsNordenfelt P, Moore TI, Mehta SB, Kalappurakkal JMathew, Swaminathan V, Koga N, Lambert TJ, Baker D, Waters JC, Oldenbourg R, Tani T, Mayor S, Waterman CM, Springer TA
JournalNat Commun
Date Published2017 Dec 11

Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here, we test whether the integrin, when engaged to an extracellular ligand and the cytoskeleton, adopts a specific orientation dictated by the direction of actin flow on the surface of migrating cells. We insert GFP into the rigid, ligand-binding head of the integrin, model with Rosetta the orientation of GFP and its transition dipole relative to the integrin head, and measure orientation with fluorescence polarization microscopy. Cytoskeleton and ligand-bound integrins orient in the same direction as retrograde actin flow with their cytoskeleton-binding β-subunits tilted by applied force. The measurements demonstrate that intracellular forces can orient cell surface integrins and support a molecular model of integrin activation by cytoskeletal force. Our results place atomic, Å-scale structures of cell surface receptors in the context of functional and cellular, μm-scale measurements.

Alternate JournalNat Commun
PubMed ID29229906
PubMed Central IDPMC5725580
Grant ListR01 GM114274 / GM / NIGMS NIH HHS / United States
R01 GM092802 / GM / NIGMS NIH HHS / United States
R01 GM100160 / GM / NIGMS NIH HHS / United States
R01 CA031798 / CA / NCI NIH HHS / United States
R37 CA031798 / CA / NCI NIH HHS / United States
R13 GM085967 / GM / NIGMS NIH HHS / United States