Molecular Biology of the Cell

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Vol. 11, Issue 8, 2793-2802, August 2000

Differential Modulation of Cadherin-mediated Cell-Cell Adhesion by Platelet Endothelial Cell Adhesion Molecule-1 Isoforms through Activation of Extracellular Regulated Kinases

Nader Sheibani,* Christine M. Sorenson, and William A. Frazier

Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110

The role of platelet endothelial cell adhesion molecule-1 (PECAM-1) in endothelial cell-cell interactions and its contribution to cadherin-mediated cell adhesion are poorly understood. Such studies have been difficult because all known endothelial cells express PECAM-1. We have used Madin-Darby canine kidney (MDCK) cells as a model system in which to evaluate the role of PECAM-1 isoforms that differ in their cytoplasmic domains in cell-cell interactions. MDCK cells lack endogenous PECAM-1 but form cell-cell junctions similar to those of endothelial cells, in which PECAM-1 is concentrated. MDCK cells were transfected with two isoforms of murine PECAM-1, Delta 15 and Delta 14&15, the predominant isoforms expressed in vivo. Expression of the Delta 15 isoform resulted in apparent dedifferentiation of MDCK cells concomitant with the loss of adherens junctions, down-regulation of E-cadherin, alpha - and beta -catenin expression, and sustained activation of extracellular regulated kinases. The Delta 15 isoform was not concentrated at cell-cell contacts. In contrast, the Delta 14&15 isoform localized to sites of cell-cell contact and had no effect on MDCK cell morphology, cadherin/catenin expression, or extracellular regulated kinase activity. Thus, the presence of exon 14 in the cytoplasmic domain of PECAM-1 has dramatic effects on the ability of cells to maintain adherens junctions and an epithelial phenotype. Therefore, changes in the expression of exon 14 containing PECAM-1 isoforms, which we have observed during development, may have profound functional consequences.

* Corresponding author and present address: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Room K6/458 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792.

Molecular Biology of the Cell
Vol. 11, 2793-2802, August 2000
Copyright © 2000 by The American Society for Cell Biology


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