title: Coordinated integrin activation by actin-dependent force during T-cell migration.
abstract: For a cell to move forward it must convert chemical energy into mechanical propulsion. Force produced by actin polymerization can generate traction across the plasma membrane by transmission through integrins to their ligands. However, the role this force plays in integrin activation is unknown. Here we show that integrin activity and cytoskeletal dynamics are reciprocally linked, where actin-dependent force itself appears to regulate integrin activity. We generated fluorescent tension-sensing constructs of integrin αLβ2 (LFA-1) to visualize intramolecular tension during cell migration. Using quantitative imaging of migrating T cells, we correlate tension in the αL or β2 subunit with cell and actin dynamics. We find that actin engagement produces tension within the β2 subunit to induce and stabilize an active integrin conformational state and that this requires intact talin and kindlin motifs. This supports a general mechanism where localized actin polymerization can coordinate activation of the complex machinery required for cell migration.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Program in Cellular and Molecular Medicine, Children's Hospital Boston, 3 Blackfan Circle, Boston, Massachusetts 02115, USA.|Image and Data Analysis Core, Harvard Medical School, 240 Longwood Ave., Boston, Massachusetts 02115, USA.|Department of Clinical Sciences, Division of Infection Medicine, Faculty of Medicine, Lund University, BMC, B14, Sölvegatan 19, 22362 Lund, Sweden.
authors.forename: Pontus
authors.identifier: 0000-0002-9481-9951
authors.initials: P
authors.lastname: Nordenfelt
authors.affiliation: Image and Data Analysis Core, Harvard Medical School, 240 Longwood Ave., Boston, Massachusetts 02115, USA.
authors.forename: Hunter L
authors.initials: HL
authors.lastname: Elliott
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Program in Cellular and Molecular Medicine, Children's Hospital Boston, 3 Blackfan Circle, Boston, Massachusetts 02115, USA.
authors.forename: Timothy A
authors.identifier: 0000-0001-6627-2904
authors.initials: TA
authors.lastname: Springer
mesh_terms: D000199:Actins / Q000378:metabolism*; D020816:Amino Acid Motifs; D001665:Binding Sites; D001696:Biomechanical Phenomena; D018821:CD18 Antigens / Q000737:chemistry / Q000378:metabolism*; D002465:Cell Movement; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008954:Models, Biological; D011487:Protein Conformation; D021122:Protein Subunits / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D013718:Tensile Strength
chemical_list: D000199:Actins; D018821:CD18 Antigens; D008024:Ligands; D021122:Protein Subunits