Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin

Verfasser / Beitragende:
[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]
Ort, Verlag, Jahr:
2016
Enthalten in:
eLife, 5, p. e10130
Format:
Artikel (online)
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024 7 0 |a 10.3929/ethz-b-000113288  |2 doi 
024 7 0 |a 10.7554/eLife.10130  |2 doi 
035 |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/113288 
245 0 0 |a Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin  |h [Elektronische Daten]  |c [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] 
506 |a Open access  |2 ethresearch 
520 3 |a 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. 
540 |a Creative Commons Attribution 4.0 International  |u http://creativecommons.org/licenses/by/4.0  |2 ethresearch 
700 1 |a Theodosiou  |D Marina  |e joint author 
700 1 |a Widmaier  |D Moritz  |e joint author 
700 1 |a Böttcher  |D Ralph T.  |e joint author 
700 1 |a Rognoni  |D Emanuel  |e joint author 
700 1 |a Veelders  |D Maik  |e joint author 
700 1 |a Bharadwaj  |D Mitasha  |e joint author 
700 1 |a Lambacher  |D Armin  |e joint author 
700 1 |a Austen  |D Katharina  |e joint author 
700 1 |a Müller  |D Daniel J.; id_orcid 0000-0003-3075-0665  |e joint author 
700 1 |a Zent  |D Roy  |e joint author 
700 1 |a Fässler  |D Reinhard  |e joint author 
773 0 |t eLife  |d Cambridge : eLife Sciences Publications  |g 5, p. e10130 
856 4 0 |u http://hdl.handle.net/20.500.11850/113288  |q text/html  |z WWW-Backlink auf das Repository (Open access) 
898 |a BK010053  |b XK010053  |c XK010000 
908 |D 1  |a Journal Article  |2 ethresearch 
949 |B ETHRESEARCH  |F ETHRESEARCH  |b ETHRESEARCH  |j Journal Article  |c Open access 
950 |B ETHRESEARCH  |P 856  |E 40  |u http://hdl.handle.net/20.500.11850/113288  |q text/html  |z WWW-Backlink auf das Repository (Open access) 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Theodosiou  |D Marina  |e joint author 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Widmaier  |D Moritz  |e joint author 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Böttcher  |D Ralph T.  |e joint author 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Rognoni  |D Emanuel  |e joint author 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Veelders  |D Maik  |e joint author 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Bharadwaj  |D Mitasha  |e joint author 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Lambacher  |D Armin  |e joint author 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Austen  |D Katharina  |e joint author 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Müller  |D Daniel J.; id_orcid 0000-0003-3075-0665  |e joint author 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Zent  |D Roy  |e joint author 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Fässler  |D Reinhard  |e joint author 
950 |B ETHRESEARCH  |P 773  |E 0-  |t eLife  |d Cambridge : eLife Sciences Publications  |g 5, p. e10130