Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2016-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/10130 |
| _version_ | 1818019089496408064 |
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| author | Marina Theodosiou Moritz Widmaier Ralph T Böttcher Emanuel Rognoni Maik Veelders Mitasha Bharadwaj Armin Lambacher Katharina Austen Daniel J Müller Roy Zent Reinhard Fässler |
| author_facet | Marina Theodosiou Moritz Widmaier Ralph T Böttcher Emanuel Rognoni Maik Veelders Mitasha Bharadwaj Armin Lambacher Katharina Austen Daniel J Müller Roy Zent Reinhard Fässler |
| author_sort | Marina Theodosiou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:46:54Z |
| format | Article |
| id | doaj.art-2cebde40050a4ecca02d34409a2d9edc |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:46:54Z |
| publishDate | 2016-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-2cebde40050a4ecca02d34409a2d9edc2022-12-22T02:05:18ZengeLife Sciences Publications LtdeLife2050-084X2016-01-01510.7554/eLife.10130Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillinMarina Theodosiou0Moritz Widmaier1Ralph T Böttcher2Emanuel Rognoni3Maik Veelders4Mitasha Bharadwaj5Armin Lambacher6Katharina Austen7Daniel J Müller8Roy Zent9Reinhard Fässler10Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, Basel, SwitzerlandDepartment of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, Basel, SwitzerlandDivision of Nephrology, Department of Medicine, Vanderbilt University, Nashville, United States; Department of Medicine, Veterans Affairs Medical Center, Nashville, United StatesDepartment of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, GermanyIntegrins 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.https://elifesciences.org/articles/10130talinkindlinpaxillinintegrinfocal adhesioncell spreading |
| spellingShingle | Marina Theodosiou Moritz Widmaier Ralph T Böttcher Emanuel Rognoni Maik Veelders Mitasha Bharadwaj Armin Lambacher Katharina Austen Daniel J Müller Roy Zent Reinhard Fässler Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin eLife talin kindlin paxillin integrin focal adhesion cell spreading |
| title | Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin |
| title_full | Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin |
| title_fullStr | Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin |
| title_full_unstemmed | Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin |
| title_short | Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin |
| title_sort | kindlin 2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin |
| topic | talin kindlin paxillin integrin focal adhesion cell spreading |
| url | https://elifesciences.org/articles/10130 |
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