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

Multicellular animal development depends on integrins. These adhesion recep tors link to the actin cytoskeleton, transmitting biochemical signals and f orce during cell migration and interactions with the extracellular matrix. Many integrin-cytoskeleton connections are formed by filamins and talin. Th e beta (7) integrin tail binds strongly to filamin and supports less migrat ion, fibronectin matrix assembly and focal adhesion formation than either t he beta (1D) tail, which binds strongly to talin, or the beta (1A) tail, wh ich binds modestly to both filamin and talin. To probe the role of filamin binding, we mapped the filamin-binding site of integrin tails and identifie d 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 fibronect in matrix assembly or focal adhesion formation. Thus, tight filamin binding restricts integrin-dependent cell migration by inhibiting transient membra ne protrusion and cell polarization.