title: Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin.
abstract: Integrins require an activation step prior to ligand binding and signaling. How talin and kindlin contribute to these events in non-hematopoietic cells is poorly understood. Here we report that fibroblasts lacking either talin or kindlin failed to activate β1 integrins, adhere to fibronectin (FN) or maintain their integrins in a high affinity conformation induced by Mn(2+). Despite compromised integrin activation and adhesion, Mn(2+) enabled talin- but not kindlin-deficient cells to initiate spreading on FN. This isotropic spreading was induced by the ability of kindlin to directly bind paxillin, which in turn bound focal adhesion kinase (FAK) resulting in FAK activation and the formation of lamellipodia. Our findings show that talin and kindlin cooperatively activate integrins leading to FN binding and adhesion, and that kindlin subsequently assembles an essential signaling node at newly formed adhesion sites in a talin-independent manner.
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Theodosiou
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Widmaier
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Böttcher
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Rognoni
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Veelders
authors.affiliation: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, Basel, Switzerland.
authors.forename: Mitasha
authors.initials: M
authors.lastname: Bharadwaj
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Lambacher
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Austen
authors.affiliation: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, Basel, Switzerland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt University, Nashville, United States.|Department of Medicine, Veterans Affairs Medical Center, Nashville, United States.
authors.forename: Roy
authors.initials: R
authors.lastname: Zent
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism*; D011485:Protein Binding; D016608:Talin / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D019012:Integrin beta1; D009124:Muscle Proteins; D051419:Paxillin; D016608:Talin; C527802:kindlin-2 protein, mouse; C496077:Tln1 protein, mouse; D008345:Manganese; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: biochemistry; cell biology; cell spreading; focal adhesion; integrin; kindlin; mouse; paxillin; talin
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