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

Giulia Mana, Donatella Valdembri, Janet A. Askari, Zhenhai Li, Patrick Caswell, Cheng Zhu, Martin J. Humphries, Christoph Ballestrem, Guido Serini

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalLife Science Alliance
Issue number2
Publication statusPublished - 1 Feb 2023


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