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Published on: July 27, 2022
A novel role for integrin-linked kinase in epithelial sheet morphogenesis
Alisa Vespa1, Sudhir J A D'Souza, Lina Dagnino
1Department of Physiology and Pharmacology and Regulatory Biology and Functional Genomics Research Group, Siebens-Drake Research Institute, London, Ontario N6A 5C1, Canada.
Insights
Integrin-linked kinase (ILK) is crucial for epithelial cell-cell adhesion, independent of its known role in cell migration. ILK
Area of Science:
- Cell Biology
- Epithelial Biology
- Molecular Biology
Background:
- Integrin-linked kinase (ILK) is a protein known for its role in cell motility and interactions with the extracellular matrix.
- ILK is typically found in focal adhesions within undifferentiated epidermal keratinocytes.
- Keratinocyte differentiation, induced by calcium (Ca2+), leads to cell-cell junction formation and altered ILK distribution.
Purpose of the Study:
- To investigate the role of ILK in the formation of cell-cell junctions during keratinocyte differentiation.
- To determine if ILK's function extends beyond integrin-mediated adhesion.
Main Methods:
- Studied the translocation of ILK and adherens junction (AJ) proteins (E-cadherin, beta-catenin) in keratinocytes upon Ca2+ treatment.
- Utilized an ILK deletion mutant (ILK 191-452) that cannot localize to the cell membrane to assess its impact on cell-cell adhesion.
- Observed the formation of tight junctions (TJ) and epithelial sheet formation in cells expressing the ILK mutant.
Main Results:
- Ca2+ treatment rapidly induced the translocation of AJ proteins (E-cadherin, beta-catenin) to the cell membrane, followed by TJ proteins.
- ILK's movement kinetics mirrored that of AJ components, suggesting a role in early cell-cell contact formation.
- Expression of a non-membrane-localizing ILK mutant (ILK 191-452) inhibited E-cadherin/beta-catenin translocation, preventing AJ and TJ formation, and disrupting epithelial sheet formation.
Conclusions:
- ILK plays a novel and essential role in establishing epithelial cell-cell adhesion.
- This function of ILK is distinct from its established role in integrin-mediated adhesion and cell migration.
- ILK is critical for the proper formation and maintenance of adherens and tight junctions in epithelial cells.
Abstract:
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 (
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