caa a22 4500 528785419 20200923042742.0 cr unu---uuuuu 180924e201601 xx s 000 0 eng 10.3929/ethz-b-000113288 doi 10.7554/eLife.10130 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/113288 Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin [Elektronische Daten] [Marina Theodosiou, Moritz Widmaier, Ralph T. Böttcher, Emanuel Rognoni, Maik Veelders, Mitasha Bharadwaj, Armin Lambacher, Katharina Austen, Daniel J.; id_orcid 0000-0003-3075-0665 Müller, Roy Zent, Reinhard Fässler] Open access ethresearch 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 Mn2+. Despite compromised integrin activation and adhesion, Mn2+ 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. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Theodosiou Marina joint author Widmaier Moritz joint author Böttcher Ralph T. joint author Rognoni Emanuel joint author Veelders Maik joint author Bharadwaj Mitasha joint author Lambacher Armin joint author Austen Katharina joint author Müller Daniel J.; id_orcid 0000-0003-3075-0665 joint author Zent Roy joint author Fässler Reinhard joint author eLife Cambridge : eLife Sciences Publications 5, p. e10130 http://hdl.handle.net/20.500.11850/113288 text/html WWW-Backlink auf das Repository (Open access) BK010053 XK010053 XK010000 1 Journal Article ethresearch ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/113288 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Theodosiou Marina joint author ETHRESEARCH 700 1- Widmaier Moritz joint author ETHRESEARCH 700 1- Böttcher Ralph T. joint author ETHRESEARCH 700 1- Rognoni Emanuel joint author ETHRESEARCH 700 1- Veelders Maik joint author ETHRESEARCH 700 1- Bharadwaj Mitasha joint author ETHRESEARCH 700 1- Lambacher Armin joint author ETHRESEARCH 700 1- Austen Katharina joint author ETHRESEARCH 700 1- Müller Daniel J.; id_orcid 0000-0003-3075-0665 joint author ETHRESEARCH 700 1- Zent Roy joint author ETHRESEARCH 700 1- Fässler Reinhard joint author ETHRESEARCH 773 0- eLife Cambridge : eLife Sciences Publications 5, p. e10130