Vimentin filament controls integrin alpha 5 beta 1-mediated cell adhesion by binding to integrin through its Ser38 residue

Abstract

Regulation of integrin affinity for its ligand is essential for cell adhesion and migration. Here, we found that direct interaction of vimentin with integrin beta 1 can enhance binding of integrin alpha 5 beta 1 to its ligand, fibronectin. Conversely, blocking the interaction reduced fibronectin binding, cell migration on a fibronectin-coated surface, and neural tube closure during Xenopus embryogenesis. We also found that withaferin A (WFA), a natural compound known to inhibit vimentin function, can suppress the vimentin-integrin interaction and abolish fibronectin binding. Finally, we identified Ser38 of vimentin as a critical residue for integrin binding. Our results suggest that phosphorylation of vimentin at Ser38 may regulate the integrin-ligand interaction, thus providing a molecular basis for antivimentin therapeutic strategies.