Premium
Interaction between Alzheimer's disease βA4 precursor protein (APP) and the extracellular matrix: Evidence for the participation of heparan sulfate proteoglycans
Author(s) -
Cáceres Jorge,
Brandan Enrique
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(199705)65:2<145::aid-jcb2>3.0.co;2-u
Subject(s) - laminin , matrigel , fibronectin , extracellular matrix , heparan sulfate , proteoglycan , chemistry , chondroitin sulfate proteoglycan , amyloid precursor protein , chondroitin sulfate , perlecan , biochemistry , microbiology and biotechnology , glycosaminoglycan , binding site , extracellular , integrin , biophysics , alzheimer's disease , biology , medicine , in vitro , receptor , disease
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 × 10 −11 M and Kd 2 of 1.6 × 10 −9 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%. β‐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. J. Cell. Biochem. 65:145–158. © 1997 Wiley‐Liss, Inc.