Interaction between Alzheimer's disease βA4 precursor protein (APP) and the extracellular matrix: Evidence for the participation of heparan sulfate proteoglycans
✍ Scribed by Jorge Cáceres; Enrique Brandan
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 309 KB
- Volume
- 65
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
The interaction between the Alzheimer amyloid precursor protein (APP) and an intact extracellular matrix (ECM), matrigel, obtained from Engelbreth-Holm-Swarm tumors was evaluated. Based on quantitative analyses of the binding data obtained from solid phase binding assays, two binding sites on the ECM were identified for [ 125 I]-APP (with apparent Kd 1 of 1.0 3 10 211 M and Kd 2 of 1.6 3 10 29 M respectively). Over 70% of [ 125 I]-APP was displaced by heparin and N-desulfated heparin but not by chondroitin sulfate. Pretreatment of matrigel with heparitinase decreased the binding of [ 125 I]-APP by 80%. b-amyloid peptides (residues 1-40, 1-28, and 1-16) containing a heparin binding domain also displaced 80% of bound [ 125 I]-APP, which was totally displaced by intact APP. The binding of [ 125 I]-APP to matrigel increased by 210% with a decrease in the pH. These observations suggest that [ 125 I]-APP interacts mainly with heparan sulfate proteoglycan present in the ECM. The binding of [ 125 I]-APP to individual ECM components was also analyzed. [ 125 I]-APP was found to bind laminin and collagen type IV but not fibronectin. However, when these ECM constituents were combined, the extent of APP-binding decreased significantly, to levels comparable to those obtained with intact matrigel, suggesting that multiple interactions may occur between ECM constituents and [ 125 I]-APP. The results are discussed in terms of APP function and amyloidogenesis.