Integrin receptors are crucial for cells to sense their surroundings. αVβ3 integrin has 12 potential ligands, which are components of the extracellular matrix (ECM), including fibronectin (Fn) and vitronectin (Vn), but the mechanisms that define the selective binding to each of them are poorly understood. Now, Martin Bastmeyer, Bernhard Wehrle-Haller and colleagues (Bachmann et al., 2020) show that the ability of αVβ3 integrin to bind to Fn depends on the mechanical load the integrin itself is subjected to. Making use of a previously established binary system for ligand choice assessment, the authors find that αVβ3 integrin preferentially binds to Vn over Fn. Through modulation of actomyosin contractility, they observe that αVβ3 integrin binds only to Vn under lower mechanical load; once this mechanical load increases, conformational changes also allow for the binding of Fn, increasing ligand promiscuity. Moreover, analysis of different constitutively active forms of αVβ3 integrin revealed that increased binding to Fn still depends on high contractility even when αVβ3 integrin is already in an extended open conformation. Finally, the authors demonstrate that force-dependent ligand choice by αVβ3 integrin also applies to other ECM components, such as osteopontin and fibrinogen. Hence, this study proposes a new mechanism for the differential ligand selectivity of αVβ3 integrin that is based on mechanosensing and the extracellular context.
αVβ3 integrin feels the force when choosing ligands
αVβ3 integrin feels the force when choosing ligands. J Cell Sci 1 May 2020; 133 (9): e0904. doi:
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