title: The role of integrin-linked kinase in the molecular architecture of focal adhesions.
abstract: Integrin-mediated focal adhesions (FAs) are large, multi-protein complexes that link the actin cytoskeleton to the extracellular matrix and take part in adhesion-mediated signaling. These adhesions are highly complex and diverse at the molecular level; thus, assigning particular structural or signaling functions to specific components is highly challenging. Here, we combined functional, structural and biophysical approaches to assess the role of a major FA component, namely, integrin-linked kinase (ILK), in adhesion formation. We show here that ILK plays a key role in the formation of focal complexes, early forms of integrin adhesions, and confirm its involvement in the assembly of fibronectin-bound fibrillar adhesions. Examination of ILK-null fibroblasts by cryo-electron tomography pointed to major structural changes in their FAs, manifested as disarray of the associated actin filaments and an increase in the packing density of FA-related particles. Interestingly, adhesion of the mutant cells to the substrate required a higher ligand density than in control cells. These data indicate that ILK has a key role in integrin adhesion assembly and sub-structure, and in the regulation of the FA-associated cytoskeleton.
authors.affiliation: Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Beer-Sheva 84120, Israel.
authors.forename: Nadav
authors.initials: N
authors.lastname: Elad
authors.forename: Tova
authors.initials: T
authors.lastname: Volberg
authors.forename: Israel
authors.initials: I
authors.lastname: Patla
authors.forename: Vera
authors.initials: V
authors.lastname: Hirschfeld-Warneken
authors.forename: Carsten
authors.initials: C
authors.lastname: Grashoff
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Spatz
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Benjamin
authors.initials: B
authors.lastname: Geiger
authors.forename: Ohad
authors.initials: O
authors.lastname: Medalia
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D003599:Cytoskeleton / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000502:physiology; D022001:Focal Adhesions / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK
keywords: Cell adhesion; Correlated microscopy; Cryo-electron tomography; Focal adhesion; Integrin; Integrin-linked kinase