dc.contributor.author | Theodosiou, M | en_US |
dc.contributor.author | Widmaier, M | en_US |
dc.contributor.author | Böttcher, RT | en_US |
dc.contributor.author | Rognoni, E | en_US |
dc.contributor.author | Veelders, M | en_US |
dc.contributor.author | Bharadwaj, M | en_US |
dc.contributor.author | Lambacher, A | en_US |
dc.contributor.author | Austen, K | en_US |
dc.contributor.author | Müller, DJ | en_US |
dc.contributor.author | Zent, R | en_US |
dc.contributor.author | Fässler, R | en_US |
dc.date.accessioned | 2019-08-28T10:53:00Z | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/59362 | |
dc.description.abstract | <jats:p>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.</jats:p> | en_US |
dc.description.sponsorship | The work was supported by RO1-DK083187, RO1-DK075594, R01-DK069221 and VA Merit Award 1I01BX002196 (to RZ), by the Deutsches Zentrum für Herz-Kreislauf-Forschung, partner site Munich Heart Alliance (to RTB and RF) and by the European Research Council (Grant Agreement no. 322652), Deutsche Forschungsgemeinschaft (SFB-863) and the Max Planck Society (to RF). | en_US |
dc.language | en | en_US |
dc.language.iso | en | en_US |
dc.publisher | eLife Sciences Publications, Ltd | en_US |
dc.relation.ispartof | eLife | en_US |
dc.rights | Creative Commons Attribution License | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.title | Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin | en_US |
dc.type | Article | |
dc.rights.holder | 2016, Theodosiou et al. | |
dc.identifier.doi | 10.7554/elife.10130 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 5 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |