The βI domain promotes active β1 integrin clustering into mature adhesion sites

Modulation of integrin function is required in many physiological and pathological settings, such as angiogenesis and cancer. Integrin allosteric changes, clustering, and trafficking cooperate to regulate cell adhesion and motility on extracellular matrix proteins via mechanisms that are partly defined. By exploiting four monoclonal antibodies recognizing distinct conformational epitopes, we show that in endothelial cells (ECs), the extracellular beta I domain, but not the hybrid or I-EGF2 domain of active beta 1 integrins, promotes their FAK-regulated clustering into tensin 1- containing fibrillar adhesions and impairs their endocytosis. In this regard, the beta I domain-dependent clustering of active beta 1 integrins is necessary to favor fibronectin-elicited directional EC motility, which cannot be effectively promoted by beta 1 integrin conformational activation alone.