APP-collagen interaction is mediated by a heparin bridge mechanism.
The amyloid precursor protein (APP) is a glycoprotein consisting of at least four isoforms derived from a single gene by a process of alternative splicing. The membrane-bound forms of APP have been suggested to have adhesive properties and to mediate neural cell adhesion. Previous studies have demonstrated the ability of Fab' fragments of antibodies to extracellular domains of APP to inhibit neural cell binding to a collagen substrate, suggesting a physiological role for the collagen-binding properties of APP. The binding of APP has been demonstrated to be specific for type IV collagen, and no binding to other extracellular matrix components, including fibronectin and laminin, was detected. The APP-collagen binding appeared to be mediated by a heparin-bridge mechanism, since the binding was abolished by the addition of excess heparan or heparinase. These results were observed by both a homogenate-collagen binding assay and a cell-surface adhesion assay, thus providing further evidence for the adhesion role of APP. They also pose the question of the possible role of the heparin-binding properties of APP in the genesis of the neuritic plaques characteristic of Alzheimer's disease.
Breen
K C
KC
Department of Pharmacology, University College, Dublin, Ireland.
D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D003094:Collagen / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D019763:Heparin Lyase; D006497:Heparan Sulfate / Q000378:metabolism*; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D016564:Amyloid beta-Protein Precursor; D003094:Collagen; D016326:Extracellular Matrix Proteins; D006493:Heparin; D019763:Heparin Lyase; D006497:Heparan Sulfate; D007140:Immunoglobulin Fab Fragments; D011133:Polysaccharide-Lyases