Nature Cell Biology
3, 1060 - 1068 (2001)
Published online: 24 October 2001; | doi:10.1038/ncb1201-1060
Increased filamin binding to  -integrin cytoplasmic domains inhibits cell migrationDavid A. Calderwood1, Anna Huttenlocher2, William B. Kiosses1, David M. Rose1, Darren G. Woodside1, Martin A. Schwartz1
& Mark H. Ginsberg1, 31
Department of Vascular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, California 92037, USA
2
Departments of Pediatrics and Pharmacology, University of Wisconsin, 1300 University Ave, Madison, Wisconsin 53706, USA
3
Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA
Correspondence should be addressed to Mark H. Ginsberg ginsberg@scripps.eduMulticellular 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  7 integrin tail binds strongly to filamin and supports less migration, fibronectin matrix assembly and focal adhesion formation than either the 1D tail, which binds strongly to talin, or the 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 7 tail and gain of filamin binding to the 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.
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4 integrins modifies integrin-dependent biological responses
