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Affinity Purification of Proteoglycans that bind to the Amyloid Protein Precursor of Alzheimers Disease

Citation

Williamson, TG and Nurcombe, V and Beyreuther, K and Masters, CL and Small, DH, Affinity Purification of Proteoglycans that bind to the Amyloid Protein Precursor of Alzheimers Disease, Journal of Neurochemistry, 65, (5) pp. 2201-2208. ISSN 0022-3042 (1995) [Refereed Article]


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The definitive published version is available online at: http://www3.interscience.wiley.com/

DOI: doi:10.1046/j.1471-4159.1995.65052201.x

Abstract

The binding of the amyloid protein precursor (APP) to heparan sulfate proteoglycans has been shown to stimulate the neurite-promoting activity of APP. In this study, proteoglycans that bind with high affinity to APP were characterized. Conditioned medium from cultures of postnatal day 3 mouse brain cells was applied to an affinity column containing a peptide homologous to a heparin-binding domain of APP. A fraction 17-fold enriched in proteoglycans was recovered by elution with a salt gradient. APP bound saturably and with high affinity to the affinity-purified proteoglycan fraction. Scatchard analysis of the binding showed that APP bound to high- and low-affinity sites with equilibrium dissociation constants of 1.4 10−11 and 6.5 10−10M, respectively. APP, in conjunction with the affinity-purified proteoglycan fraction, promoted neurite outgrowth. The affinity-purified proteoglycan fraction contained a heparan sulfate proteoglycan and a chondroitin sulfate proteoglycan. Digestion of the affinity-purified fraction with heparitinase I revealed a core protein of 6369-kDa molecular mass, whereas digestion with chondroitinase ABC revealed a core protein of 100110 kDa. The results suggest that expression of specific APP-binding proteoglycans may be an important step in the regulation of the neurite outgrowth-promoting activity of APP.

Item Details

Item Type:Refereed Article
Keywords: Extracellular matrix; Neurite outgrowth; Heparin
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Small, DH (Professor David Small)
ID Code:75424
Year Published:1995
Web of Science® Times Cited:30
Deposited By:Research Division
Deposited On:2012-01-30
Last Modified:2012-02-01
Downloads:0

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