Binding of ZO-1 to α5β1 integrins regulates the mechanical properties of α5β1-fibronectin links

Mol Biol Cell. 2017 Jul 7;28(14):1847-1852. doi: 10.1091/mbc.E17-01-0006. Epub 2017 Mar 1.

Abstract

Fundamental processes in cell adhesion, motility, and rigidity adaptation are regulated by integrin-mediated adhesion to the extracellular matrix (ECM). The link between the ECM component fibronectin (fn) and integrin α5β1 forms a complex with ZO-1 in cells at the edge of migrating monolayers, regulating cell migration. However, how this complex affects the α5β1-fn link is unknown. Here we show that the α5β1/ZO-1 complex decreases the resistance to force of α5β1-fn adhesions located at the edge of migrating cell monolayers while also increasing α5β1 recruitment. Consistently with a molecular clutch model of adhesion, this effect of ZO-1 leads to a decrease in the density and intensity of adhesions in cells at the edge of migrating monolayers. Taken together, our results unveil a new mode of integrin regulation through modification of the mechanical properties of integrin-ECM links, which may be harnessed by cells to control adhesion and migration.

MeSH terms

  • Animals
  • CHO Cells
  • Cell Adhesion / physiology
  • Cell Movement
  • Cricetulus
  • Extracellular Matrix / metabolism
  • Fibronectins / metabolism
  • Fibronectins / physiology
  • Humans
  • Integrin alpha5beta1 / metabolism*
  • Integrin alpha5beta1 / physiology
  • Integrins / metabolism
  • Mechanotransduction, Cellular / physiology
  • Protein Binding
  • Zonula Occludens-1 Protein / metabolism*
  • Zonula Occludens-1 Protein / physiology

Substances

  • FN1 protein, human
  • Fibronectins
  • Integrin alpha5beta1
  • Integrins
  • TJP1 protein, human
  • Zonula Occludens-1 Protein