Integrin α4β1 signaling modulates cell spreading and migration by dynamic regulation of paxillin expression

Abstract

Leukocyte adhesion and migration are fundamental processes in immune responses, relying on the precise spatiotemporal regulation of integrin-mediated signaling. Although paxillin is known to function as a crucial adaptor protein in adhesion complexes, how its expression is regulated during dynamic cell motility remains unclear. Here, we report that integrin α4β1 ligand binding triggers a rapid transient transcriptional upregulation of paxillin during T cell adhesion and spreading. This response is mediated through FAK/AKT/NF-κB signaling, as inhibition of any component in this axis suppresses paxillin induction and impairs cell motility. Elevated paxillin further strengthens its interaction with integrin α4 tail, resulting in decreased cell spreading and driving efficient cell migration. These results reveal a previously unrecognized transcriptional regulatory circuit that enables leukocytes to rapidly adapt their adhesive machinery during immune surveillance, offering insights into integrin regulatory networks.