Vimentin Tunes Cell Migration On Collagen By Controlling Beta 1 Integrin Activation And Clustering

Vimentin is a structural protein that is required for mesenchymal cell migration and directly interacts with actin, beta 1 integrin and paxillin. We examined how these interactions enable vimentin to regulate cell migration on collagen. In fibroblasts, depletion of vimentin increased talin-dependent activation of beta 1 integrin by more than 2-fold. Loss of vimentin was associated with reduction of beta 1 integrin clustering by 50% and inhibition of paxillin recruitment to focal adhesions by more than 60%, which was restored by vimentin expression. This reduction of paxillin was associated with 65% lower Cdc42 activation, a 60% reduction of cell extension formation and a greater than 35% decrease in cell migration on collagen. The activation of PAK1, a downstream effector of Cdc42, was required for vimentin phosphorylation and filament maturation. We propose that vimentin tunes cell migration through collagen by acting as an adaptor protein for focal adhesion proteins, thereby regulating beta 1 integrin activation, resulting in well-organized, mature integrin clusters.