Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation
- Takao Sakai1,
- Shaohua Li2,
- Denitsa Docheva1,
- Carsten Grashoff1,
- Keiko Sakai1,
- Günter Kostka1,
- Attila Braun1,
- Alexander Pfeifer3,
- Peter D. Yurchenco2, and
- Reinhard Fässler1,4
- 1Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany; 2Department of Pathology and Medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA; 3Department of Pharmacy, Center for Drug Research, University of Munich, 81377 Munich, Germany
Abstract
Integrin-mediated cell–matrix interactions are essential for development, tissue homeostasis, and repair. Upon ligand binding, integrins are recruited into focal adhesions (FAs). Integrin-linked kinase (ILK) is an FA component that interacts with the cytoplasmic domains of integrins, recruits adaptor proteins that link integrins to the actin cytoskeleton, and phosphorylates the serine/threonine kinases PKB/Akt and GSK-3β. Here we show that mice lacking ILK expression die at the peri-implantation stage because they fail to polarize their epiblast and to cavitate. The impaired epiblast polarization is associated with abnormal F-actin accumulation at sites of integrin attachments to the basement membrane (BM) zone. Likewise, ILK-deficient fibroblasts showed abnormal F-actin aggregates associated with impaired cell spreading and delayed formation of stress fibers and FAs. Finally, ILK-deficient fibroblasts have diminished proliferation rates. However, insulin or PDGF treatment did not impair phosphorylation of PKB/Akt and GSK-3β, indicating that the proliferation defect is not due to absent or reduced ILK-mediated phosphorylation of these substrates in vivo. Furthermore, expression of a mutant ILK lacking kinase activity and/or paxillin binding in ILK-deficient fibroblasts can rescue cell spreading, F-actin organization, FA formation, and proliferation. Altogether these data show that mammalian ILK modulates actin rearrangements at integrin-adhesion sites.
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Footnotes
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↵4 Corresponding author.
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E-MAIL faessler{at}biochem.mpg.de; FAX 49-89-8578-2422.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.255603.
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- Received November 19, 2002.
- Accepted February 10, 2003.
- Cold Spring Harbor Laboratory Press