QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 9, 4084-4095, September 2005

This Article Full Text Full Text (PDF) All Versions of this Article: E05-02-0087v1 16/9/4084    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vespa, A. Articles by Dagnino, L. Search for Related Content PubMed PubMed Citation Articles by Vespa, A. Articles by Dagnino, L.

A Novel Role for Integrin-linked Kinase in Epithelial Sheet Morphogenesis

Alisa Vespa ^*, Sudhir J.A. D'Souza ^*, and Lina Dagnino ^* 

^* Department of Physiology and Pharmacology and Regulatory Biology and Functional Genomics Research Group, Siebens-Drake Research Institute, London, Ontario N6A 5C1, Canada; Department of Paediatrics, University of Western Ontario, London, Ontario N6A 5C1, Canada

Submitted February 1, 2005; Revised June 7, 2005; Accepted June 10, 2005
Monitoring Editor: Asma Nusrat

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 Ca²⁺ triggers formation of cell–cell junctions, loss of focal adhesions, and ILK distribution to cell borders. We now show that Ca²⁺ treatment of keratinocytes induces rapid (1 h) translocation to the cell membrane of the adherens junction (AJ) proteins E-cadherin and -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/-catenin to cell borders, precluding Ca²⁺-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.

Abbreviations used: AJ, adherens junction(s); DTT, dithiothreitol; ECM, extracellular matrix; EMEM, Eagle's minimum essential medium; FBS, fetal bovine serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFP, green fluorescent protein; IP, immunoprecipitation; ILK, integrin-linked kinase; PBS, phosphate-buffered saline; PMSF, phenylmethylsulfonyl fluoride; TJ, tight junction(s).

Address correspondence to: Lina Dagnino (ldagnino{at}uwo.ca) or Sudhir J.A. D'Souza (sjdsouza{at}uwo.ca).

This article has been cited by other articles:

				K.-A. Nakrieko, I. Welch, H. Dupuis, D. Bryce, A. Pajak, R. St. Arnaud, S. Dedhar, S. J. A. D'Souza, and L. Dagnino Impaired Hair Follicle Morphogenesis and Polarized Keratinocyte Movement upon Conditional Inactivation of Integrin-linked Kinase in the Epidermis Mol. Biol. Cell, April 1, 2008; 19(4): 1462 - 1473. [Abstract] [Full Text] [PDF]

				K. Lorenz, C. Grashoff, R. Torka, T. Sakai, L. Langbein, W. Bloch, M. Aumailley, and R. Fassler Integrin-linked kinase is required for epidermal and hair follicle morphogenesis J. Cell Biol., May 7, 2007; 177(3): 501 - 513. [Abstract] [Full Text] [PDF]