Secreted glypican binds to the amyloid precursor protein of Alzheimer's disease (APP) and inhibits APP-induced neurite outgrowth.

The Journal of Biological Chemistry
T WilliamsonDavid H Small

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 substrate-bound 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-beta-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 prot...Continue Reading

References

Jul 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·L A Greene, A S Tischler
Jan 1, 1992·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·A D SnowT N Wight
Oct 15, 1992·Biochemical and Biophysical Research Communications·L KarthikeyanR U Margolis
Nov 27, 1991·Biochemical and Biophysical Research Communications·W ArakiJ Kimura
Jan 1, 1990·Journal of Cellular Physiology·D Gurwitz, D D Cunningham
Jan 1, 1988·Annual Review of Biochemistry·M A Ferguson, A F Williams
Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
May 16, 1984·Biochemical and Biophysical Research Communications·G G Glenner, C W Wong
Aug 28, 1995·Brain Research. Developmental Brain Research·H J ClarrisD H Small
Oct 15, 1993·Brain Research. Developmental Brain Research·M OhtaJ Tateishi
Mar 1, 1995·The Journal of Cell Biology·B AllinquantA Prochiantz

❮ Previous
Next ❯

Citations

Jan 23, 1998·Developmental Dynamics : an Official Publication of the American Association of Anatomists·E D LitwackA D Lander
Jul 20, 2002·Peptides·Geneviève Evin, Andreas Weidemann
Aug 30, 2003·Neuroscience Letters·Seita HaginoAkio Wanaka
Jul 25, 2003·Lancet Neurology·Jack van HorssenMarcel M Verbeek
Jan 17, 2009·Cell Death and Differentiation·F C LourençoP Mehlen
Dec 10, 1999·The Biochemical Journal·Y ParkR J Linhardt
May 24, 2007·PloS One·Gabriel del RioDale E Bredesen
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·L BakiN K Robakis
Feb 18, 2016·Oxidative Medicine and Cellular Longevity·Beata PająkArkadiusz Orzechowski
Apr 27, 2016·Aging and Disease·Stephanie PlummerRoberto Cappai
Jul 24, 2015·Molecular Neurodegeneration·Vivek GautamDora M Kovacs
Mar 19, 2015·Frontiers in Cellular Neuroscience·Ilaria CanobbioGiordano Pula
Jan 15, 2014·International Journal of Alzheimer's Disease·Sara H MokhtarSteven Petratos
Nov 24, 2016·Neurochemical Research·A R JayakumarM D Norenberg
Apr 7, 2017·Journal of Neurochemistry·Saket M NigamMark P Mattson
Jan 1, 1997·Critical Reviews in Biochemistry and Molecular Biology·R Kisilevsky, P E Fraser
May 27, 2014·Journal of Structural Biology·Sandra HoefgenManuel E Than
Sep 30, 1998·The European Journal of Neuroscience·J G SchulzU Dirnagl
Nov 1, 2013·World Journal of Psychiatry·Geneviève Evin, Qiao-Xin Li
Feb 28, 2003·Journal of Neuroscience Research·M Teresa Moreno-FloresFrancisco Wandosell
Dec 17, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Alan E MastDennis J Dietzen
Apr 24, 1999·Neuropathology and Applied Neurobiology·E Storey, R Cappai
Sep 17, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lucas J SosaKarl H Pfenninger
Sep 14, 2014·The Journal of Biological Chemistry·Marta BolósDavid H Small

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