The present address of Dr. H. Ninomiya is Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606, Japan.
Secreted Form of Amyloid β/A4 Protein Precursor (APP) Binds to Two Distinct APP Binding Sites on Rat B103 Neuron-Like Cells Through Two Different Domains, but Only One Site Is Involved in Neuritotropic Activity
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 63, Issue 2, pages 495–500, August 1994
How to Cite
Ninomiya, H., Roch, J.-M., Jin, L.-W. and Saitoh, T. (1994), Secreted Form of Amyloid β/A4 Protein Precursor (APP) Binds to Two Distinct APP Binding Sites on Rat B103 Neuron-Like Cells Through Two Different Domains, but Only One Site Is Involved in Neuritotropic Activity. Journal of Neurochemistry, 63: 495–500. doi: 10.1046/j.1471-4159.1994.63020495.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received September 2, 1993; revised manuscript received December 1, 1993; accepted December 13, 1993.
- Alzheimer's disease;
- Neuritotropic activity;
- Amyloid β/A4 protein precursor
Abstract: Recent studies have identified the Alzheimer's disease amyloid β/A4 protein precursor (APP) as a trophic and/or tropic protein on several types of cells, including fibroblasts, primary culture neurons, PC12 cells, and B103 neuron-like cells. Many trophic proteins bind heparin, and it is believed that the heparin-binding domain is crucial for the trophic activity of these proteins. APP also binds heparin. The current studies were undertaken to examine the hypothesis that the neuritotropic activity of APP requires heparin binding. It was found that APP produced in E. coli bound B103 cells through detergent-extractable molecules. Approximately 50% of the binding sites were heparinase-sensitive, and heparin and heparan sulfate competed for APP binding to these sites. The heparinase-insensitive sites were recognized by a stretch of 17 amino acids of APP (residues 319–335) that contains the neuritotropic activity of APP. A mutant APP with a deletion at this site was capable of binding to the heparinase-sensitive sites, although this molecule was not neuritotropic to B103 neuron-like cells. Therefore, the neuritotropic site and the heparin-binding site are distinct in APP, and the neuritotropic effect of APP is produced through its binding to detergent-extractable and heparinase-insensitive sites.