C. elegans PAT-4/ILK functions as an adaptor protein within integrin adhesion complexes.
BACKGROUND
Mammalian integrin-linked kinase (ILK) was identified in a yeast two-hybrid screen for proteins binding the integrin beta(1) subunit cytoplasmic domain. ILK has been implicated in integrin-mediated signaling and is also an adaptor within integrin-associated cytoskeletal complexes.


RESULTS
We identified the C. elegans pat-4 gene in previous genetic screens for mutants unable to assemble integrin-mediated muscle cell attachments. Here, we report that pat-4 encodes the sole C. elegans homolog of ILK. In pat-4 null mutants, embryonic muscle cells form integrin foci, but the subsequent recruitment of vinculin and UNC-89 as well as actin and myosin filaments to these in vivo focal adhesion analogs is blocked. Conversely, PAT-4/ILK requires the ECM component UNC-52/perlecan, the transmembrane protein integrin, and the novel cytoplasmic attachment protein UNC-112 to be properly recruited to nascent attachments. Transgenically expressed "kinase-dead" ILK fully rescues pat-4 loss-of-function mutants. We also identify UNC-112 as a new binding partner for ILK.


CONCLUSIONS
Our data strengthens the emerging view that ILK functions primarily as an adaptor protein within integrin adhesion complexes and identifies UNC-112 as a new ILK binding partner.
Mackinnon
A Craig
AC
Department of Cell and Structural Biology, University of Illinois, Urbana-Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, USA.
Qadota
Hiroshi
H
Norman
Kenneth R
KR
Moerman
Donald G
DG
Williams
Benjamin D
BD
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D022001:Focal Adhesions; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D046911:Macromolecular Substances; D009132:Muscles / Q000166:cytology / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D009154:Mutation; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D016596:Vinculin / Q000378:metabolism; D000099200:Scaffold Protein ILK
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D019812:Heparan Sulfate Proteoglycans; D016023:Integrins; D046911:Macromolecular Substances; D017346:Protein Serine-Threonine Kinases; D016596:Vinculin; D000099200:Scaffold Protein ILK; C411729:UNC-112 protein, C elegans; C071927:perlecan; C466238:PAT-4 protein, C elegans