Membrane curvature and dynamin2 activation promotes integrin-beta3 endocytosis at the podosome

Abstract

Cell adhesions are the signalling hubs to render biophysical events to cellular functions. Podosomes are cell-matrix adhesion structures and comprise protrusive F-actin polymerization surrounded by ring-shaped integrin-mediated adhesions. Integrin-beta3 is one of the key adhesion molecules at the podosome and binds to RGD motif in the extracellular matrix. While the activation and turnover of integrin-beta3 play important role in adhesion formation, the mechanism of integrin-beta3 endocytosis on the cell membrane remains unclear. Here, we use a model system of viscous RGD-membrane to investigate the functional role of podosome in integrin-beta3 endocytosis. We find that the levels of internalized RGD are positively correlated with the podosome assembly on RGD membranes. Protrusive F-actin polymerization causes membrane invagination of integrin-beta3 receptors at the podosome ring. BAR-domain protein BIN1 is recruited to invaginated membrane and activates dynamin2-mediated endocytosis of RGD-integrin clusters at the podosome. Inhibitions of BIN1-dynamin2 signalling axis suppress the endocytosis of RGD ligand and cell migration. Thus, podosome assembly triggers membrane deformation and dynamin2 activation and promotes the endocytosis of integrin-beta3.