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First published online 28 February 2006
doi: 10.1242/jcs.02827

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Displacement of the ß cytoplasmic domain recovers focal adhesion formation, cytoskeletal organization and motility in swapped integrin chimeras

Michael A. Partridge^*, Frank S. David^*, and Eugene E. Marcantonio

Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA

Author for correspondence (e-mail: eem2{at}columbia.edu)

Accepted 6 December 2005

Integrin-mediated `outside-in' signaling requires the transmission of a conformational change from the extracellular domains to the cytoplasmic domains. Although one component of this conformational change is the separation of the and ß cytoplasmic domains, it is not clear how this separation could result in the initiation of downstream signals necessary for focal adhesion (FA) formation. To address this question, we used a swapped integrin heterodimer, in which the extracellular domains of the and ß chains were attached to their opposing transmembrane and cytoplasmic domains. This receptor was able to bind ligand normally, but could not promote FA formation. We then displaced the ß cytoplasmic domain with either a duplication of its membrane-proximal region or an unrelated -helical spacer. This displacement partially restored FA formation in these swapped receptors and rescued other aspects of integrin-mediated signaling, including cytoskeletal organization, motility and several tyrosine-phosphorylation-dependent signals. We suggest that separation of the cytoplasmic domains leads to alteration of the secondary structure of the distal ß tail, which initiates downstream signals leading to cytoskeletal reorganization.

Key words: Integrin, Focal adhesions, Cell motility, Outside-in signals

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