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Secreted Glypican Binds to the Amyloid Precursor Protein of Alzheimer's Disease (APP) and Inhibits APP-induced Neurite Outgrowth
Citation
Williamson, TG and Mok, SS and Henry, A and Cappai, R and Lander, AD and Nurcombe, V and Beyreuther, K and Masters, CL and Small, DH, Secreted Glypican Binds to the Amyloid Precursor Protein of Alzheimer's Disease (APP) and Inhibits APP-induced Neurite Outgrowth, Journal of Biological Chemistry, 271, (49) pp. 31215-31221. ISSN 0021-9258 (1996) [Refereed Article]
DOI: doi:10.1074/jbc.271.49.31215
Abstract
The amyloid precursor protein (APP) of Alzheimer’s
disease has been shown to stimulate neurite outgrowth
in vitro. The effect of APP on neurite outgrowth can be
enhanced if APP is presented to neurons in substratebound
form, in the presence of heparan sulfate proteoglycans.
To identify specific heparan sulfate proteoglycans
that bind to APP, conditioned medium from
neonatal mouse brain cells was subjected to affinity
chromatography with recombinant APP695 as a ligand.
Glypican bound strongly to the APP affinity column.
Purified glypican bound to APP with an equilibrium
dissociation constant of 2.8 nM and inhibited APP-induced
neurite outgrowth from chick sympathetic neurons.
The effect of glypican was specific for APP, as
glypican did not inhibit laminin-induced neurite outgrowth.
Furthermore, treatment of cultures with
4-methylumbelliferyl-�-D-xyloside, a competitive inhibitor
of proteoglycan glycanation, inhibited APP-induced
neurite outgrowth but did not inhibit laminin-induced
neurite outgrowth. This result suggests that endogenous
proteoglycans are required for substrate-bound
APP to stimulate neurite outgrowth. Secreted glypican
may act to inhibit APP-induced neurite outgrowth in
vivo by competing with endogenous proteoglycans for
binding to APP.
Item Details
Item Type: | Refereed Article |
---|---|
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Neurosciences |
Research Field: | Neurosciences not elsewhere classified |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Small, DH (Professor David Small) |
ID Code: | 71710 |
Year Published: | 1996 |
Web of Science® Times Cited: | 89 |
Deposited By: | Menzies Institute for Medical Research |
Deposited On: | 2011-08-02 |
Last Modified: | 2011-10-12 |
Downloads: | 0 |
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