TY - JOUR T1 - The βI domain promotes active β1 integrin clustering into mature adhesion sites JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201388 VL - 6 IS - 2 SP - e202201388 AU - Giulia Mana AU - Donatella Valdembri AU - Janet A Askari AU - Zhenhai Li AU - Patrick Caswell AU - Cheng Zhu AU - Martin J Humphries AU - Christoph Ballestrem AU - Guido Serini Y1 - 2023/02/01 UR - https://www.life-science-alliance.org/content/6/2/e202201388.abstract N2 - 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 βI domain, but not the hybrid or I-EGF2 domain of active β1 integrins, promotes their FAK-regulated clustering into tensin 1–containing fibrillar adhesions and impairs their endocytosis. In this regard, the βI domain–dependent clustering of active β1 integrins is necessary to favor fibronectin-elicited directional EC motility, which cannot be effectively promoted by β1 integrin conformational activation alone. ER -