title: Activation-enhanced alpha(IIb)beta(3)-integrin-cytoskeleton interactions outside of focal contacts require the alpha-subunit.
abstract: Integrins link the cell's cytoskeleton to the extracellular matrix, as well as to receptors on other cells. These links occur not only at focal contacts but also at smaller integrin-containing protein complexes outside of focal contacts. We previously demonstrated the importance of focal contact-independent integrin-cytoskeleton interactions of beta(2) integrins: activation of adhesion resulted from a release of integrins from cytoskeletal constraints. To determine whether changes in integrin-cytoskeleton interactions were related to activation of the integrin, we used single particle tracking to examine focal contact-independent cytoskeletal associations of alpha(IIb)beta(3)-integrin, in which activation results in a large conformational change. Direct activation of alpha(IIb)beta(3) by mutation did not mimic activation of lymphocytes with phorbol ester, because it enhanced integrin-cytoskeleton interactions, whereas activation of lymphocytes decreased them. Using additional integrin mutants, we found that both alpha- and beta-cytoplasmic domains were required for these links. This suggests that 1) both beta(2)- and beta(3)-integrins interact with the cytoskeleton outside of focal contacts; 2) activation of a cell and activation of an integrin are distinct processes, and both can affect integrin-cytoskeleton interactions; and 3) the role of the alpha-subunit in integrin-cytoskeleton interactions in at least some circumstances is more direct than generally supposed.
authors.affiliation: Research Service, Birmingham Veterans Administration Medical Center, Birmingham, Alabama 35294, USA. kucik@uab.edu
authors.forename: D F
authors.initials: DF
authors.lastname: Kucik
authors.forename: T E
authors.initials: TE
authors.lastname: O'Toole
authors.forename: A
authors.initials: A
authors.lastname: Zheleznyak
authors.forename: D K
authors.initials: DK
authors.lastname: Busettini
authors.forename: E J
authors.initials: EJ
authors.lastname: Brown
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003599:Cytoskeleton / Q000378:metabolism*; D004058:Diffusion; D022001:Focal Adhesions / Q000378:metabolism; D008024:Ligands; D008863:Microspheres; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021122:Protein Subunits
chemical_list: D008024:Ligands; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D021122:Protein Subunits