title: Displacement of the {beta} cytoplasmic domain recovers focal adhesion formation, cytoskeletal organization and motility in swapped integrin chimeras.
abstract: 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 alpha and beta 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 alpha and beta 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 beta cytoplasmic domain with either a duplication of its membrane-proximal region or an unrelated alpha-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 beta tail, which initiates downstream signals leading to cytoskeletal reorganization.
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Partridge
authors.forename: Frank S
authors.initials: FS
authors.lastname: David
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Marcantonio
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D006224:Cricetinae; D022001:Focal Adhesions; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D016023:Integrins; D011993:Recombinant Fusion Proteins