Platelet/endothelial cell adhesion molecule-1 (CD31)-mediated cellular aggregation involves cell surface glycosaminoglycans.
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.
DeLisser
H M
HM
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Yan
H C
HC
Newman
P J
PJ
Muller
W A
WA
Buck
C A
CA
Albelda
S M
SM
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002449:Cell Aggregation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA; D004277:DNA, Single-Stranded; D006025:Glycosaminoglycans / Q000378:metabolism*; D007739:L Cells / Q000166:cytology; D051379:Mice; D008969:Molecular Sequence Data; D019408:Platelet Endothelial Cell Adhesion Molecule-1
D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D004277:DNA, Single-Stranded; D006025:Glycosaminoglycans; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D004247:DNA