Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • Pontus Nordenfelt
  • Travis I Moore
  • Shalin B Mehta
  • Joseph Mathew Kalappurakkal
  • Vinay Swaminathan
  • Nobuyasu Koga
  • Talley J Lambert
  • David Baker
  • Jennifer C Waters
  • Rudolf Oldenbourg
  • Tomomi Tani
  • Satyajit Mayor
  • Clare M Waterman
  • Timothy A Springer
Enheter & grupper
Externa organisationer
  • University of Washington, Seattle
  • Harvard Medical School
  • Marine Biological Laboratory
  • University of Washington
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
Originalspråkengelska
Artikelnummer2047
TidskriftNature Communications
Volym8
Utgivningsnummer1
StatusPublished - 2017 dec 11
PublikationskategoriForskning
Peer review utfördJa