title: A central multifunctional role of integrin-linked kinase at muscle attachment sites.
abstract: Integrin-linked kinase (ILK) is an essential component of a multiprotein complex that links actin to the plasma membrane. Here, we have used a genetic approach to examine the molecular interactions that are essential for the assembly of this ILK-containing complex at Drosophila muscle attachment sites (MASs). We show that, downstream of integrins, talin plays a decisive role in the recruitment of three proteins: ILK, PINCH and paxillin. The accumulation of ILK at MASs appears to follow an amplification mechanism, suggesting that numerous binding sites are generated by minimal levels of the upstream integrin and talin effectors. This property suggests that ILK functions as an essential hub in the assembly of its partner proteins at sites of integrin adhesion. We found that PINCH stability, and its subcellular localization at MASs, depends upon ILK function, but that ILK stability and localization is not dependent upon PINCH. An in vivo structure-function analysis of ILK demonstrated that each ILK domain has sufficient information for its independent recruitment at embryonic MASs, whereas at later developmental stages only the kinase domain was effectively recruited. Our data strengthen the view that the ILK complex is assembled sequentially at sites of integrin adhesion by employing multiple molecular interactions, which collectively stabilize the integrin-actin link.
authors: Biomedical Research Foundation, Academy of Athens, Division of Genetics, Soranou Efessiou 4, 11527 Athens, Greece. czervas@bioacademy.gr
authors: Christos G
authors: CG
authors: Zervas
authors: Eleni
authors: E
authors: Psarra
authors: Victoria
authors: V
authors: Williams
authors: Esther
authors: E
authors: Solomon
authors: Katerina M
authors: KM
authors: Vakaloglou
authors: Nicholas H
authors: NH
authors: Brown
mesh_terms: D000818:Animals; D004330:Drosophila / Q000196:embryology / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D009132:Muscles / Q000737:chemistry / Q000196:embryology / Q000201:enzymology* / Q000378:metabolism; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D000099200:Scaffold Protein ILK
chemical_list: D016023:Integrins; D051419:Paxillin; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK