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Platelet/endothelial cell adhesion molecule-1 (CD31)-mediated cellular aggregation involves cell surface
H M DeLisser1, H C Yan, P J Newman
1Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
The Journal of Biological Chemistry
|July 25, 1993
Summary
Platelet/endothelial cell adhesion molecule-1 (PECAM-1) mediates cell aggregation through binding specific glycosaminoglycans on adjacent cells. This interaction is crucial and involves a key binding sequence in the second immunoglobulin-like domain of PECAM-1.
Area of Science:
- Cellular Biology
- Molecular Biology
- Immunology
Background:
- Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is an integral membrane glycoprotein found on endothelial cells, platelets, and leukocytes.
- PECAM-1 facilitates calcium-dependent heterophilic aggregation in cells expressing its cDNA.
Purpose of the Study:
- To investigate the specific ligand interactions driving PECAM-1-mediated cell aggregation.
- To identify the molecular mechanisms and domains involved in PECAM-1's adhesive function.
Main Methods:
- Studied PECAM-1-mediated aggregation using transfected mouse L-cells.
- Assessed the effect of various glycosaminoglycans (GAGs) and enzymatic GAG removal on aggregation.
- Utilized mutant PECAM-1 proteins lacking specific domains and synthetic peptides mimicking binding sequences.
Main Results:
- PECAM-1-mediated aggregation was inhibited by heparin and chondroitin sulfate, indicating a specific GAG interaction.
- Enzymatic removal of cell surface GAGs confirmed PECAM-1's interaction with GAGs on adjacent cells.
- A consensus GAG binding sequence in PECAM-1's second immunoglobulin-like domain was identified as critical for aggregation; mutations or peptide inhibition disrupted this process.
Conclusions:
- PECAM-1-mediated cell aggregation relies on the direct binding of PECAM-1 to specific glycosaminoglycans on neighboring cells.
- The second immunoglobulin-like domain of PECAM-1, containing a consensus GAG binding sequence, is essential for mediating these adhesive interactions.