Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation

Takao Sakai, Shaohua Li, Denitsa Docheva, Carsten Grashoff, Keiko Sakai, Günter Kostka, Attila Braun, Alexander Pfeifer, Peter D. Yurchenco, Reinhard Fässler

Research output: Contribution to journalArticlepeer-review

301 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)926-940
Number of pages15
JournalGenes and Development
Volume17
Issue number7
DOIs
StatePublished - Apr 1 2003

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Keywords

  • Epiblast
  • Integrin
  • Integrin-linked kinase (ILK)
  • Knockout

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