Alternative splicing of a specific cytoplasmic exon alters the binding characteristics of murine platelet/endothelial cell adhesion molecule-1 (PECAM-1).

Yan HC, Baldwin HS, Sun J, Buck CA, Albelda SM, DeLisser HM
J Biol Chem. 1995 270 (40): 23672-80

PMID: 7559536 · DOI:10.1074/jbc.270.40.23672

Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a membrane glycoprotein expressed on endothelial cells, platelets, and leukocytes. Analysis of PECAM-1 expression in the developing mouse embryo has revealed the presence of multiple isoforms of murine PECAM-1 (muPECAM-1) that appeared to result from the alternative splicing of exons encoding cytoplasmic domain sequences (exons 10-16) (Baldwin, H. S., Shen, H. M., Yan, H., DeLisser, H. M., Chung, A., Mickanin, C., Trask, T., Kirschbaum, N. E. Newman, P. J., Albelda, S., and Buck, C. A. (1994) Development 120, 2539-2553). To investigate the functional consequences of alternatively spliced muPECAM-1 cytoplasmic domains, L-cells were transfected with cDNA for each variant and their ability to promote cell aggregation was compared. In this assay, full-length muPECAM-1 and all three isoforms containing exon 14 behaved like human PECAM-1 in that they mediated calcium- and heparin-dependent heterophilic aggregation. In contrast, three muPECAM-1 variants, all missing exon 14, mediated calcium- and heparin-independent homophilic aggregation. Exon 14 thus appears to modulate the ligand and adhesive interactions of the extracellular domain of PECAM-1. These findings suggest that alternative splicing may represent a mode of regulating the adhesive function of PECAM-1 in vivo and provides direct evidence that alternative splicing involving the cytoplasmic domain affects the ligand specificity and binding properties of a cell adhesion receptor.

MeSH Terms (28)

Alternative Splicing Amino Acid Sequence Animals Antibodies, Monoclonal Antigens, Differentiation, Myelomonocytic Base Sequence Blood Platelets Cell Adhesion Molecules Cell Aggregation Cloning, Molecular Cytoplasm DNA, Complementary DNA Primers Embryo, Mammalian Endothelium, Vascular Exons Genetic Variation Glycosylation Humans L Cells Ligands Mice Molecular Sequence Data Platelet Endothelial Cell Adhesion Molecule-1 Protein Binding Sequence Deletion Sequence Homology, Nucleic Acid Transfection

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