Platelet/endothelial cell adhesion molecule-1 (CD31)-mediated cellular aggregation involves cell surface glycosaminoglycans

• Published in: The Journal of biological chemistry Vol. 268; no. 21; pp. 16037 - 16046
• Main Authors: DELISSER, H. M, HORNG CHIN YAN, NEWMAN, P. J, MULLER, W. A, BUCK, C. A, ALBELDA, S. M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25.07.1993
• Subjects: 3T3 Cells; Amino Acid Sequence; Animals; Antigens, Differentiation, Myelomonocytic - genetics; Antigens, Differentiation, Myelomonocytic - metabolism; Base Sequence; Binding Sites; Biological and medical sciences; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Aggregation; Cell interactions, adhesion; Cell Membrane - metabolism; Cells, Cultured; DNA; DNA, Single-Stranded; Fundamental and applied biological sciences. Psychology; Glycosaminoglycans - metabolism; L Cells - cytology; Mice; Molecular and cellular biology; Molecular Sequence Data; Platelet Endothelial Cell Adhesion Molecule-1; Aggregation; Endothelial cell; Platelet; Cell adhesion molecule; Glycosaminoglycan; Molecular interaction; Binding site
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)82354-7

Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a 130-kDa integral membrane glycoprotein expressed on endothelial cells, platelets, and leukocytes. Experiments analyzing the aggregation of mouse L-cells stably transfected with full-length PECAM-1 cDNA have demonstrated that PECAM-1 is capable of mediating calcium-dependent heterophilic aggregation. In this report the ligand interactions involved in the aggregation process were studied. This aggregation was inhibited by heparin and chondroitin sulfate, but not by other glycosaminoglycans. Enzymatic removal of cell surface glycosaminoglycans confirmed a PECAM-1-glycosaminoglycan interaction and suggested that this interaction involved glycosaminoglycans on adjacent cells. PECAM-1 contains a glycosaminoglycan consensus binding sequence in the second immunoglobulin-like domain of the molecule's extracellular domain. A comparable region in the related adhesion protein N-CAM has been shown to mediate the adhesive properties of N-CAM. Cells expressing mutant PECAM-1 protein missing the second domain failed to aggregate. Synthetic peptides mimicking the consensus glycosaminoglycan binding sequence, L-K-R-E-K-N, inhibited aggregation. These results demonstrate that PECAM-1-mediated aggregation is dependent on the binding of PECAM-1 to specific glycosaminoglycans on adjacent cells via a glycosaminoglycan consensus binding sequence in the second immunoglobulin-like homology domain.