A novel role for integrin-linked kinase in epithelial sheet morphogenesis.
Integrin-linked kinase (ILK) is a multidomain protein involved in cell motility and cell-extracellular matrix interactions. ILK is found in integrin-containing focal adhesions in undifferentiated primary epidermal keratinocytes. Induction of keratinocyte differentiation by treatment with Ca(2+) triggers formation of cell-cell junctions, loss of focal adhesions, and ILK distribution to cell borders. We now show that Ca(2+) treatment of keratinocytes induces rapid (<or=1 h) translocation to the cell membrane of the adherens junction (AJ) proteins E-cadherin and beta-catenin. This is followed by slower (>6 h) localization of tight junction (TJ) proteins. The kinetics of ILK movement toward the cell periphery mimics that of AJ components, suggesting that ILK plays a role in the early formation of cell-cell contacts. Whereas the N terminus in ILK mediates localization to cell borders, expression of an ILK deletion mutant incapable of localizing to the cell membrane (ILK 191-452) interferes with translocation of E-cadherin/beta-catenin to cell borders, precluding Ca(2+)-induced AJ formation. Cells expressing ILK 191-452 also fail to form TJ and sealed cell-cell borders and do not form epithelial sheets. Thus, we have uncovered a novel role for ILK in epithelial cell-cell adhesion, independent of its well-established role in integrin-mediated adhesion and migration.
Department of Physiology and Pharmacology and Regulatory Biology and Functional Genomics Research Group, Siebens-Drake Research Institute, London, Ontario N6A 5C1, Canada.
Alisa
A
Vespa
Sudhir J A
SJ
D'Souza
Lina
L
Dagnino
D022005:Adherens Junctions / Q000502:physiology; D000818:Animals; D017089:Ankyrin Repeat; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004848:Epithelium / Q000201:enzymology*; D019084:Fluorescent Antibody Technique, Indirect; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology; D000099200:Scaffold Protein ILK
D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK