title: Alternative splicing of a specific cytoplasmic exon alters the binding characteristics of murine platelet/endothelial cell adhesion molecule-1 (PECAM-1).
abstract: 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.
authors.affiliation: Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104-4283, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Yan
authors.forename: H S
authors.initials: HS
authors.lastname: Baldwin
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: C A
authors.initials: CA
authors.lastname: Buck
authors.forename: S M
authors.initials: SM
authors.lastname: Albelda
authors.forename: H M
authors.initials: HM
authors.lastname: DeLisser
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D001792:Blood Platelets / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D002449:Cell Aggregation; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004622:Embryo, Mammalian; D004730:Endothelium, Vascular / Q000378:metabolism; D005091:Exons; D014644:Genetic Variation; D006031:Glycosylation; D006801:Humans; D007739:L Cells; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011485:Protein Binding; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D018076:DNA, Complementary; D008024:Ligands; D019408:Platelet Endothelial Cell Adhesion Molecule-1