Increased filamin binding to β-integrin cytoplasmic domains inhibits cell migration

Multicellular animal development depends on integrins. These adhesion receptors link to the actin cytoskeleton, transmitting biochemical signals and force during cell migration and interactions with the extracellular matrix. Many integrin-cytoskeleton connections are formed by filamins and talin. The beta (7) integrin tail binds strongly to filamin and supports less migration, fibronectin matrix assembly and focal adhesion formation than either the beta (1D) tail, which binds strongly to talin, or the beta (1A) tail, which binds modestly to both filamin and talin. To probe the role of filamin binding, we mapped the filamin-binding site of integrin tails and identified amino acid substitutions that led to selective loss of filamin binding to the beta (7) tail and gain of filamin binding to the beta (1A) tail. These changes affected cell migration and membrane protrusions but not fibronectin matrix assembly or focal adhesion formation. Thus, tight filamin binding restricts integrin-dependent cell migration by inhibiting transient membrane protrusion and cell polarization.