Browsing by Author "Caceres, J"

Now showing 1 - 1 of 1
  • No Thumbnail Available
    Item
    Interaction between Alzheimer's disease beta A4 precursor protein (APP) and the extracellular matrix: Evidence for the participation of heparan sulfate proteoglycans
    (1997) Caceres, J; Brandan, E
    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 [I-125]-APP (with apparent Kd(1) of 1.0 x 10(-11) M and Kd(2) of 1.6 x 10(-9) M respectively). Over 70% of [I-125]-APP was displaced by heparin and N-desulfated heparin but not by chondroitin sulfate. Pretreatment of matrigel with heparitinase decreased the binding of [I-125]-APP by 80%. beta-amyloid peptides (residues 1-40, 1-28, and 1-16) containing a heparin binding domain also displaced 80% of bound [I-125]-APP, which was totally displaced by intact APP. The binding of [I-125]-APP to matrigel increased by 210% with a decrease in the pH. These observations suggest that [I-125]-APP interacts mainly with heparan sulfate proteoglycan present in the ECM. The binding of [I-125]-APP to individual ECM components was also analyzed. [I-125]-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 [I-125]-APP. The results are discussed in terms of APP function and amyloidogenesis. (C) 1997 Wiley-Liss, Inc.