title: Deletions in the cytoplasmic domain of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) result in changes in ligand binding properties.
abstract: Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a member of the immunoglobulin superfamily present on platelets, endothelial cells, and leukocytes that may function as a vascular cell adhesion molecule. The purpose of this study was to examine the role of the cytoplasmic domain in PECAM-1 function. To accomplish this, wild-type and mutated forms of PECAM-1 cDNA were transfected into murine fibroblasts and the functional characteristics of the cells analyzed. Wild-type PECAM-1 localized to the cell-cell borders of adjacently transfected cells and mediated heterophilic, calcium-dependent L-cell aggregation that was inhibitable by a polyclonal and two monoclonal anti-PECAM-1 antibodies. A mutant protein lacking the entire cytoplasmic domain did not support aggregation or move to cell-cell borders. In contrast, both forms of PECAM-1 with partially truncated cytoplasmic domains (missing either the COOH-terminal third or two thirds of the cytoplasmic domain) localized to cell-cell borders in 3T3 cells in a manner analogous to the distribution seen in cultured endothelial cells. L-cells expressing these mutants demonstrated homophilic, calcium-independent aggregation that was blocked by the polyclonal anti-PECAM-1 antibody, but not by the two bioactive monoclonal antibodies. Although changes in the cytoplasmic domain of other receptors have been shown to alter ligand-binding affinity, to our knowledge, PECAM-1 is the first example of a cell adhesion molecule where changes in the cytoplasmic domain result in a switch in the basic mechanism of adhesion leading to different ligand-binding specificity. Variations in the cytoplasmic domain could thus be a potential mechanism for regulating PECAM-1 activity in vivo.
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: H M
authors.initials: HM
authors.lastname: DeLisser
authors.forename: J
authors.initials: J
authors.lastname: Chilkotowsky
authors.forename: H C
authors.initials: HC
authors.lastname: Yan
authors.forename: M L
authors.initials: ML
authors.lastname: Daise
authors.forename: C A
authors.initials: CA
authors.lastname: Buck
authors.forename: S M
authors.initials: SM
authors.lastname: Albelda
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry* / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D002451:Cell Compartmentation; D003593:Cytoplasm / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011485:Protein Binding; D011940:Receptor Aggregation; D011994:Recombinant Proteins; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D008024:Ligands; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins