title: Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation.
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-3beta. 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-3beta, 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.
authors.affiliation: Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany.
authors.forename: Takao
authors.initials: T
authors.lastname: Sakai
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
authors.forename: Denitsa
authors.initials: D
authors.lastname: Docheva
authors.forename: Carsten
authors.initials: C
authors.lastname: Grashoff
authors.forename: Keiko
authors.initials: K
authors.lastname: Sakai
authors.forename: Günter
authors.initials: G
authors.lastname: Kostka
authors.forename: Attila
authors.initials: A
authors.lastname: Braun
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
authors.forename: Peter D
authors.initials: PD
authors.lastname: Yurchenco
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology*; D005434:Flow Cytometry; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D000099200:Scaffold Protein ILK
chemical_list: D000199:Actins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK