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

Theodosiou, M., Widmaier, M., Böttcher, R. T., Rognoni, E., Veelders, M., Bharadwaj, M., et al. (2016). Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin. ELIFE, 5: e10130. doi:10.7554/eLife.10130.

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 Creators:
Theodosiou, Marina1, Author              
Widmaier, Moritz1, Author              
Böttcher, Ralph T.1, Author              
Rognoni, Emanuel1, Author              
Veelders, Maik1, Author              
Bharadwaj, Mitasha2, Author
Lambacher, Armin1, Author              
Austen, Katharina3, Author              
Müller, Daniel J.2, Author
Zent, Roy2, Author
Fässler, Reinhard1, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2external, ou_persistent22              
3Grashoff, Carsten / Molecular Mechanotransduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565150              

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Free keywords: FOCAL ADHESION KINASE; PLATELET-AGGREGATION; FORCE SPECTROSCOPY; NASCENT ADHESIONS; DIVALENT-CATIONS; GENE-EXPRESSION; CATCH BONDS; ILK-COMPLEX; ALPHA(5)BETA(1); FIBRONECTIN
 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 pi 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.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published online
 Pages: 24
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000369061200001
DOI: 10.7554/eLife.10130
 Degree: -

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Title: ELIFE
Source Genre: Journal
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Publ. Info: SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND : ELIFE SCIENCES PUBLICATIONS LTD
Pages: - Volume / Issue: 5 Sequence Number: e10130 Start / End Page: - Identifier: ISSN: 2050-084X